| 2016 |
Sandra Cohen (P) |
Hôpital Maisonneuve-Rosemont |
Subventions de soutien des essais cliniques |
Cohen |
Chercheur principal |
Sandra Cohen |
999 968 |
Making cord blood hematopoietic stem cell expansion competitive |
Sang |
|
Allogeneic hematopoietic stem cell (HSC) transplant is the best available therapy to cure blood cancers. Unfortunately, 1/3 of patients do not have a matched donor (related or unrelated). Cord blood (CB) is an attractive alternative donor source due to its unique properties, including permissive mismatches, low incidence of chronic graft-versus-host disease (cGVHD) and rapid availability. A lower risk of cGVHD is very important as it is the major determinant of long-term quality of life after transplant. However, these advantages are offset by the limited cell dose (i.e. small cords), which results in delayed- or non-engraftment (recovery of blood counts), increased infections, prolonged hospitalization and early mortality. In February 2016 we launched a CB expansion clinical trial to translate to the clinic 2 Canadian discoveries, a compound developed in G. Sauvageau and A. Marinier’s laboratory (UM171) and a bioreactor system (fed-batch) from P. Zandstra’s laboratory. Combined together these ground-breaking technologies aim to increase the HSC content of CBs and reduce the associated complications.
Our long-term objective is to design newly engineered CB grafts which will combine rapid (<12 days) engraftment with maximal anti-tumor effect (cord blood T cells) and minimal side effects (low transplant related mortality and GVHD). To achieve this, we have brought together a Canadian multidisciplinary team with state-of-the-art expertise in stem cell biology, immunology, bioengineering, cell therapy and clinical transplantation.
We seek financial support to recruit additional patients to our ongoing trial to dramatically increase the competitiveness of our strategy. We will introduce 2 modifications in our manufacturing protocol, significantly reducing cost and increasing efficacy. Consequently, we will be able to initiate a minor modification in our transplantation procedure that will minimize the risk of acute GVHD, a complication that remains too frequent. In parallel, a socio-economical study will allow us to best position our expansion strategy within Canada and internationally.
Once completed, results from this trial will be transferred to our commercial vector ExCellThera, a recently created Canadian biotech. All these improvements should make expanded CB a very desirable product for patients as well as for society and could challenge the current gold standard of matched related and unrelated donor transplants. In 3-4 years we should be in a position to initiate a multicenter enlarged phase II trial to confirm efficacy and efficiency of our product, which could be paradigm changing in the field of HSC transplantation. |
01/12/2016 |
31/12/2017 |
| 2016 |
Duncan Stewart (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien des essais cliniques |
Stewart |
Chercheur principal |
Duncan Stewart |
999 546 |
Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT-AMI) |
Cardiaque |
|
Rationale: Patients with a large area of damaged heart muscle after a heart attack have a high risk for heart failure and death. Cell-based gene therapy could restore working muscle in regions that otherwise would form only scar, and lead to better heart repair and function.
Purpose: The primary objectives of the ENACT-AMI trial are to determine whether the administration of a patient’s own (autologous) Endothelial Progenitor Cells (EPCs) is safe and effective in improving cardiac function following large heart attack, and whether the use of cells that are genetically engineered by adding extra copies of a gene that is critical for blood vessel function and repair, namely endothelial Nitric Oxide Synthase (eNOS), is superior to non-modified cells. A secondary objective is to determine whether the benefit of EPC therapy depends on the timing of cell delivery (5-15 days versus 16-30 days post-STEMI).
Novel aspects: The use of the patient’s own cells avoids the immunological rejection that occurs with transplantation of cells from other individuals, but is greatly hampered by the fact that the reparative activities of stem and progenitor cells are negatively influenced by the host risk factors that lead to heart disease in the first place, namely advanced age, high cholesterol, diabetes and so forth. We have shown that adding extra copies of the eNOS gene (which protects blood vessels and promotes their growth and repair) can restore the activity of EPCs from heart patients by almost 90%. ENACT-AMI is the first clinical trial in the world to include a strategy designed to enhance the function of a patient’s own cells, and the first to use combination gene and cell therapy, for the treatment of heart disease.
Benefits to Canadians and Canada: While outcomes after heart attacks have greatly improved with the advent of modern therapies to open up the blocked coronary artery (reperfusion therapy), about 20% of patients fail to receive the expected benefits of reperfusion therapy, and face the consequences of large heart damage and subsequent heart failure. Should gene-enhanced EPCs provide an effective adjunctive treatment for these patients, this would avoid a high individual burden of chronic debilitating disease, while reducing the high costs to the health care system which in Canada totals $2.8 billion per year for heart failure (heartandstroke.ca/heartreport). If successful, ENACT investigators are well positioned to disseminate such a therapy across Canada though CellCAN, a unique network of cell manufacturing facilities across Canada. |
01/12/2016 |
31/12/2017 |
| 2016 |
Harold Atkins (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien des essais cliniques |
Atkins |
Chercheur principal |
Harold Atkins |
215 700 |
Using hematopoietic stem cell transplantation to regenerate a naïve immunie system tolerant to liver allografts |
Insuffisance hépatique |
|
Although short-term results for liver transplantation are excellent, the need for immunosuppression limits quality of life and long-term survival. Many transplant patients develop post-transplant complications including renal failure, cardiovascular disease, neoplasms, and life-threatening infections. The ability to induce a state of operational tolerance, that is, graft acceptance without the need for long-term immunosuppression, would be a major advance in the field, cutting the ongoing costs of immune suppression and reducing medical complications of organ transplantation and the associated costs to the health care system.
We propose an open-label, non-regulated, REB approved, proof-of-principle trial to determine whether immunological tolerance can be created following ablation of pre-existing allograft reactive immunity and regeneration of a naive immune system from an autologous hematopoietic stem cell transplant, in recipients of a liver allograft.
By 31-December-2017, we propose to complete the intervention on 10 patients. Safety data would be available on 9 patients and preliminary efficacy data on 7 patients. By the end of the following year, safety and 1 year efficacy data would be available on all 10 recipients. Correlative studies will examine the composition and functionality of the regenerated immune system, the nature of tolerance (or reactivity) to the liver allograft and whether a previously reported gene signature can predict tolerance to the liver graft.
Key team members include Dr. G Levy directing the liver transplant team at University Health Network and Dr. H Atkins directing the HSCT team at The Ottawa Hospital. Key partners include Novartis, which is supplying Everolimus, a regulatory T cell expanding agent, for the trial and the Birmingham Foundation, which is helping defray patient living expenses. A test for determining immunological tolerance is a potential commercial offshoot of this work.
Positive results, that is 50% or more of the patients are free from rejection without immune suppression, would provide sufficient evidence to confirm the results in a randomized Phase IIB trial and would support additional Phase IIA trials testing the ability of auHSCT to generate tolerant immune systems in other (kidney, heart…) allograft recipients. Future studies would also test the ability to regenerate self-tolerant immune systems for patients with autoimmune liver diseases – potentially preventing endstage organ damage and the need for liver transplantation. |
01/12/2016 |
31/12/2017 |
| 2016 |
Lauralyn McIntyre (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien des essais cliniques |
McIntyre |
Chercheur principal |
Lauralyn McIntyre |
1 000 000 |
Cellular Immunotherapy for Septic Shock (CISS): A Phase II Multicentre Clinical Trial |
Septicémie |
|
Septic shock is a devastating illness and the most severe form of infection seen in the intensive care unit (ICU). It is common, with severe repercussions—each year in Canada, approximately 100,000 patients will be admitted with septic shock to an ICU and 20–40% will die. Survivors suffer long-term impairment in function and reduced quality of life. Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy, at a cost of approximately 4-billion dollars annually. Mesenchymal stem cells (MSCs) represent a novel treatment. In animal models, MSCs have been shown to calm the immune system, rid infection-causing organisms, restore organ function, and reduce death.
Over the last 5 years, our team has taken the lead to develop a research program studying MSCs in septic shock. Our team is the first in the World to have conducted and completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe in critical acutely ill patients and that a randomized controlled trial is feasible. Based on this, we are now moving to a larger clinical trial at several academic hospitals across Canada. This Phase II trial will continue to evaluate safety and assess if there are strong signals for clinical benefit as well as determine mechanisms by which MSCs exert their positive effects. An economic analysis will also determine if the treatment is cost effective.
Our multi-disciplinary team consists of a world leader in regenerative medicine and cellular therapy, internationally recognized sepsis and stem cell basic scientists, senior methodologists, clinical trialists, a health economist, stem cell manufacturing and processing experts, and a patient representative. We are collaborating with the Canadian Critical Care Trials Group and Translational Biology Group, a prolific group of world-renowned investigators, and have established partnerships within the Ottawa Hospital Research Institute and Canadian Blood Services to develop a highly potent cryopreserved MSC product and to ensure its efficient distribution to all of our participating centres. A strong signal for clinical benefit in the Phase II trial will be used to secure industrial partnership to support a definitive international multi-centre Phase III cell therapy trial which if positive could result in saving thousands of lives and restoring the function and quality of life of survivors of this devastating illness. |
01/12/2016 |
31/12/2017 |
| 2016 |
James Shapiro (P) |
University of Alberta |
Subventions de soutien des essais cliniques |
Shapiro |
Chercheur principal |
James Shapiro |
499 596 |
Clinical trials in stem cell transplantation - solving the supply and the survival problem in Type 1 diabetes |
Diabète |
|
Diabetes is the 7th leading cause of death in North America, the leading cause of renal failure, non-traumatic limb amputations, and new cases of blindness in adults. Mortality rates of Canadians with diabetes are almost twice those without the disease. The burden to our healthcare system is staggering, with annual diabetes costs of $1.1 billion.
Presently there is no known cure. Considering the disadvantages of current available treatments, we propose the following two clinical trials (VC-01 and Autologous CD34+ Stem Cell Therapy trials) that we anticipate will contribute to more efficient and cost-effective novel treatments to T1DM and some T2DM:
• VC-01 Trial to treat patients with longstanding T1DM
The goal of this trial is to evaluate a potentially limitless source of human embryonic stem cell derived new β -cells, as a substitute for clinical islet transplantation from cadaveric donors, in a first-in human clinical study. ViaCyte Inc. has led the field with consistent progress in the development of a clinically applicable β -cell line. Ultimately, this cell source could be used to restore β -cell mass in patients with T1DM and T2DM.
Hypothesis:
Transplantation of PEC-01 stem cell derived β-cells will mature in patients with T1DM, secrete insulin in response to glucose, and be sufficiently potent to reduce or eliminate the need for exogenous insulin. When implanted within an immunoisolating device (Encaptra®), no immunosuppression will be required.
If successful, it would be perceived as a major step forward towards a durable T1DM cure.
• Autologous CD34+ Stem Cell Therapy Trial to restore self-tolerance and drive β -cell regeneration without need for immunosuppression in patients with new-onset T1DM.
The goal of this trial is to demonstrate that subjects with new-onset T1DM undergoing autologous hematopoetic stem cell mobilization and immunologic reset will have greater preservation of endogenous insulin secretion compared to controls, and foremost that the treatment is safe, without myeloablation or need for chronic immunosuppression
Hypothesis:
T-depletional and anti-inflammatory treatment will restore self-tolerance in T1DM and mobilization of autologous CD34+ stem cells coupled with a long-acting glucagon-like Peptide-1 (GLP-1) analogue, will promote pancreatic islet regeneration and repair in the absence of myeloablation.
There has been remarkable progress in understanding the potential role of sub-populations of bone marrow derived stem cells in facilitating tissue repair. Coupled with ‘immunologic reset’ to disrupt autoimmunity, this approach offers tremendous curative potential in T1DM. A large collaboration team has been established for these two trials. |
01/12/2016 |
31/12/2017 |
| 2016 |
Timothy Kieffer (P) |
University of British Columbia |
Subventions de soutien des essais cliniques |
Kieffer |
Chercheur principal |
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere |
35 431 |
A stem cell therapy for insulin replacement in patients with diabetes |
Diabète |
|
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history. |
01/12/2016 |
31/12/2017 |
| 2016 |
David Thompson (C) |
University of British Columbia |
Subventions de soutien des essais cliniques |
Kieffer |
Cochercheur |
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere |
185 021 |
A stem cell therapy for insulin replacement in patients with diabetes |
Diabète |
|
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history. |
01/12/2016 |
31/12/2017 |
| 2016 |
Garth Warnock (C) |
University of British Columbia |
Subventions de soutien des essais cliniques |
Kieffer |
Cochercheur |
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere |
82 000 |
A stem cell therapy for insulin replacement in patients with diabetes |
Diabète |
|
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history. |
01/12/2016 |
31/12/2017 |
| 2016 |
Graydon Meneilly (C) |
University of British Columbia |
Subventions de soutien des essais cliniques |
Kieffer |
Cochercheur |
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere |
115 548 |
A stem cell therapy for insulin replacement in patients with diabetes |
Diabète |
|
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history. |
01/12/2016 |
31/12/2017 |
| 2016 |
Megan Levings (C) |
University of British Columbia |
Subventions de soutien des essais cliniques |
Kieffer |
Cochercheur |
Timothy Kieffer, Garth Warnock, Graydon Meneilly, Megan Levings, David Thompson, Bruce Verchere |
82 000 |
A stem cell therapy for insulin replacement in patients with diabetes |
Diabète |
|
Diabetes results from insufficient production of the glucose lowering hormone insulin from pancreatic islet cells. Severe forms of the disease used to be fatal until Canadians discovered insulin in 1921 and developed methods to purify it to provide a source for patients to inject. While life-sustaining, many patients with diabetes face a life-long routine of daily insulin injections and blood glucose measurements and suffer from several debilitating complications of the disease that severely reduce quality of life. Cell replacement therapy using islet cells obtained from organ donors has proven to be a highly effective treatment for diabetes. In fact, some islet recipients are completely insulin-independent five years after their transplant, and some even remain insulin-independent as long as ten years. However, use of this therapy is severely restricted due to a limited supply of donor organs and the high cost of the procedure. Stem cell-derived islet replacement can overcome both the supply and cost limitations of cadaveric islet replacement. The California company ViaCyte is developing a pancreatic progenitor product from human stem cells that represents a renewable, cost-effective source of cells for islet replacement. Moreover, ViaCyte has developed a device that can contain the cells and is designed for implant under the skin. Clinical testing of this potential product is now underway, and initial results with low doses of cells indicate the procedure is safe.
In this project the Vancouver team aims to recruit patients with type 1 diabetes to examine if higher doses of the cells can restore normal control of blood glucose levels and reduce, or even eliminate, the need for insulin injections. The team consists of surgeon Dr. Garth Warnock, the first to successfully transplant donor islets in patients in Canada, and co-developer of the so-called “Edmonton Protocol” for islet transplant, clinicians Dr. David Thompson and Dr. Graydon Meneilly who are experts in diabetes management and will carefully follow the patients enrolled in the trial, Dr. Megan Levings, a world-renowned immunologist who will monitor patients for immune responses to the implanted cells, and project leader Dr. Timothy Kieffer, an authority on cell therapy for diabetes whose laboratory research on stem cells provides strong scientific support for the trial. If successful, this clinical trial may lead to the development of a product that can cure millions of patients with diabetes, putting an end to insulin injections and making another major accomplishment in Canada’s diabetes research history. |
01/12/2016 |
31/12/2017 |
| 2016 |
Liam Brunham (P) |
University of British Columbia |
Recherche d’impact, clinical translation |
Brunham |
Chercheur principal |
Liam Brunham, Glen Tibbits |
50 000 |
Using human pluripotent stem-cell derived cardiomycytes to investigate the mechanisms of ibrutinib-induced atrial fibrilation |
Cardiaque; fibrillation auriculaire |
|
Ibrutinib is a new, highly effective medication used to treat blood cancers. However, up to 10% of patients receiving this medication develop an abnormal heart rhythm, called atrial fibrillation (AF) that can cause stroke. How Ibrutinib causes AF is unknown.
Human pluripotent stem cells (hPSCs) can be used to generate human heart cells (cardiomyocytes). We have shown that hPSC-derived cardiomyocytes are an excellent model system for studying drug-induced heart injury. The overall goal of this project is to use hPSC-derived cardiomyocytes to investigate the mechanisms of ibrutinib-induced AF.
We have developed unique technologies that will allow us to study this important question. This includes the ability to make cardiomyocytes representing the different heart chambers (atrial and ventricular), and to study electrical activity in cardiomyocytes. We have partnered with the Heart & Stroke Foundation of Canada for this work.
The outcomes of this study will be a novel stem cell-based model of ibrutinib-induced AF which will provide insights into the mechanisms of this side-effect, allowing us to predict which patients may be most sensitive to ibrutinib, and identify medications to treat or prevent AF in patients who receive ibrutinib, ultimately making treatment with this important new drug safer and more effective. |
01/12/2016 |
31/12/2017 |
| 2016 |
Glen Tibbits (C) |
Simon Fraser University |
Recherche d’impact, clinical translation |
Brunham |
Cochercheur |
Liam Brunham, Glen Tibbits |
50 000 |
Using human pluripotent stem-cell derived cardiomycytes to investigate the mechanisms of ibrutinib-induced atrial fibrilation |
Cardiaque; fibrillation auriculaire |
|
Ibrutinib is a new, highly effective medication used to treat blood cancers. However, up to 10% of patients receiving this medication develop an abnormal heart rhythm, called atrial fibrillation (AF) that can cause stroke. How Ibrutinib causes AF is unknown.
Human pluripotent stem cells (hPSCs) can be used to generate human heart cells (cardiomyocytes). We have shown that hPSC-derived cardiomyocytes are an excellent model system for studying drug-induced heart injury. The overall goal of this project is to use hPSC-derived cardiomyocytes to investigate the mechanisms of ibrutinib-induced AF.
We have developed unique technologies that will allow us to study this important question. This includes the ability to make cardiomyocytes representing the different heart chambers (atrial and ventricular), and to study electrical activity in cardiomyocytes. We have partnered with the Heart & Stroke Foundation of Canada for this work.
The outcomes of this study will be a novel stem cell-based model of ibrutinib-induced AF which will provide insights into the mechanisms of this side-effect, allowing us to predict which patients may be most sensitive to ibrutinib, and identify medications to treat or prevent AF in patients who receive ibrutinib, ultimately making treatment with this important new drug safer and more effective. |
01/12/2016 |
31/12/2017 |
| 2016 |
Jean-Philip Lumb (C) |
Université McGill |
Recherche d’impact, clinical translation |
Crist |
Cochercheur |
Jean-Philip Lumb, Colin Crist |
23 400 |
Activation of muscle stem cells by pharmacological inhibitors of elF2a phosphorylation |
Muscle, muscles |
|
There are few treatment options available for muscle wasting associated with cancer (cachexia), which affects roughly 50% of all cancer patients in Canada and has a major impact on morbidity and mortality. Cancer cachexia will benefit from the development of stem cell based therapies that promote the activity of endogenous muscle stem cells (MuSCs) to repair and contribute to new muscle. In healthy muscle, adult muscle stem cells are normally in a resting state and activate in response to muscle injury to repair muscle. Pharmacological approaches to activate muscle stem cells, or improve their intrinsic capacity to repair muscle are needed. We have demonstrated that normally resting muscle stem cells require tightly regulated levels of protein synthesis. Using genetic tools to inactivate pathways regulating protein synthesis, we demonstrate the spontaneous activation of muscle stem cells to generate new myofibres. These findings provide the conceptual basis for the current study, which aims to use pharmacological inhibition of pathways regulating protein synthesis to activate and improve the generation of myofibres from defective muscle stem cells in cachectic muscle. Using mouse models that permit the tracking of activated muscle stem cells by their expression of a red fluorescent protein, we will test known inhibitors of pathways regulating protein synthesis for their ability to activate muscle stem cells. Inhibitors that activate muscle stem cells are also expected to improve their activity under conditions that normally prevent their efficient contribution to repair, which will be tested in a preclinical mouse model of cancer cachexia. |
01/12/2016 |
31/12/2017 |
| 2016 |
Colin Crist (P) |
Jewish General Hospital |
Recherche d’impact, clinical translation |
Crist |
Chercheur principal |
Jean-Philip Lumb, Colin Crist |
76 442 |
Activation of muscle stem cells by pharmacological inhibitors of elF2a phosphorylation |
Muscle, muscles |
|
There are few treatment options available for muscle wasting associated with cancer (cachexia), which affects roughly 50% of all cancer patients in Canada and has a major impact on morbidity and mortality. Cancer cachexia will benefit from the development of stem cell based therapies that promote the activity of endogenous muscle stem cells (MuSCs) to repair and contribute to new muscle. In healthy muscle, adult muscle stem cells are normally in a resting state and activate in response to muscle injury to repair muscle. Pharmacological approaches to activate muscle stem cells, or improve their intrinsic capacity to repair muscle are needed. We have demonstrated that normally resting muscle stem cells require tightly regulated levels of protein synthesis. Using genetic tools to inactivate pathways regulating protein synthesis, we demonstrate the spontaneous activation of muscle stem cells to generate new myofibres. These findings provide the conceptual basis for the current study, which aims to use pharmacological inhibition of pathways regulating protein synthesis to activate and improve the generation of myofibres from defective muscle stem cells in cachectic muscle. Using mouse models that permit the tracking of activated muscle stem cells by their expression of a red fluorescent protein, we will test known inhibitors of pathways regulating protein synthesis for their ability to activate muscle stem cells. Inhibitors that activate muscle stem cells are also expected to improve their activity under conditions that normally prevent their efficient contribution to repair, which will be tested in a preclinical mouse model of cancer cachexia. |
01/12/2016 |
31/12/2017 |
| 2016 |
Bartha Knoppers (C) |
Université McGill |
Recherche d’impact, clinical translation |
Germain |
Cochercheur |
Bartha Knoppers, Lucie Germain |
10 000 |
Treatment of patients with corneal limbal stem cell deficiencies using epithelial grants |
Oculaire |
|
This project will complete our clinical trial and allows us to seek Health Canada approval for a new modality of treatment for corneal limbal stem cell deficiency (“LSCD”) using cell therapy. LSCD is a severe disease caused by damage/depletion of the corneal stem cells in the limbal region of the eye following trauma/disease. The epithelial tissue no longer regenerates resulting in chronic inflammation, conjunctivalization and vision loss. To treat LSCD patients, we have developed a tissue engineering technique involving massive expansion of epithelial cells in vitro to produce epithelial sheets for autologous transplantation (cultured epithelial corneal autografts – “CECA”). After thirty years of experience with skin substitutes using cultured epithelial autografts (“CEA”) on burn patients, we have successfully demonstrated the effectiveness of CECA (pre-clinical studies in animal models), and initiated a clinical trial approved by Health Canada (10 patients grafted with CECA on the 15 patients approved). This is the new treatment for which Health Canada approval will be sought. Our team of scientific researchers, clinicians and ethical/legal experts, with extra funding support from CHU de Québec Hospital Research Center, FRQS ThéCell Network, we will be the first in Canada to offer CECA treatment for unilaterally blind or vision impaired patients suffering from LSCD.
Le LOEX développe le génie tissulaire afin de reconstruire des tissus in vitro à des fins cliniques. La première application fût la culture de peau pour les grands brûlés. L’œil est recouvert par la cornée, qui nécessite les cellules souches limbiques, et dont la transparence est nécessaire à la vision. L’objectif du projet est de poursuivre l'essai clinique qui consiste à greffer une culture d’épithélium cornéen autologue (CECA) chez des patients souffrant d’une déficience unilatérale en cellules souches limbiques. Cette recherche translationnelle vise à finaliser l'essai clinique chez les premiers patients greffés avec CECA au Canada et à demander l'approbation de ce traitement à Santé Canada. Le projet consistera à prélever le tissu, à cultiver les cellules épithéliales du limbe in vitro sur un gel de fibrine qui sera greffé dans l’œil des patients. L’étude permettra d'effectuer la greffe des 5 derniers patients, de finaliser le suivi de 1 an de tous les patients, d’effectuer les analyses des résultats et de la faisabilité d’utiliser les CECA pour les indications proposées. Notre équipe multidisciplinaire permettra la translation clinique du produit du génie tissulaire: CECA. Nous serons les premiers au Canada à offrir ce traitement qui vise à améliorer la vision des patients. |
01/12/2016 |
31/12/2017 |
| 2016 |
Lucie Germain (P) |
Université Laval |
Recherche d’impact, clinical translation |
Germain |
Chercheur principal |
Bartha Knoppers, Lucie Germain |
90 000 |
Treatment of patients with corneal limbal stem cell deficiencies using epithelial grants |
Oculaire; déficit en cellules souches limbiques |
|
This project will complete our clinical trial and allows us to seek Health Canada approval for a new modality of treatment for corneal limbal stem cell deficiency (“LSCD”) using cell therapy. LSCD is a severe disease caused by damage/depletion of the corneal stem cells in the limbal region of the eye following trauma/disease. The epithelial tissue no longer regenerates resulting in chronic inflammation, conjunctivalization and vision loss. To treat LSCD patients, we have developed a tissue engineering technique involving massive expansion of epithelial cells in vitro to produce epithelial sheets for autologous transplantation (cultured epithelial corneal autografts – “CECA”). After thirty years of experience with skin substitutes using cultured epithelial autografts (“CEA”) on burn patients, we have successfully demonstrated the effectiveness of CECA (pre-clinical studies in animal models), and initiated a clinical trial approved by Health Canada (10 patients grafted with CECA on the 15 patients approved). This is the new treatment for which Health Canada approval will be sought. Our team of scientific researchers, clinicians and ethical/legal experts, with extra funding support from CHU de Québec Hospital Research Center, FRQS ThéCell Network, we will be the first in Canada to offer CECA treatment for unilaterally blind or vision impaired patients suffering from LSCD.
Le LOEX développe le génie tissulaire afin de reconstruire des tissus in vitro à des fins cliniques. La première application fût la culture de peau pour les grands brûlés. L’œil est recouvert par la cornée, qui nécessite les cellules souches limbiques, et dont la transparence est nécessaire à la vision. L’objectif du projet est de poursuivre l'essai clinique qui consiste à greffer une culture d’épithélium cornéen autologue (CECA) chez des patients souffrant d’une déficience unilatérale en cellules souches limbiques. Cette recherche translationnelle vise à finaliser l'essai clinique chez les premiers patients greffés avec CECA au Canada et à demander l'approbation de ce traitement à Santé Canada. Le projet consistera à prélever le tissu, à cultiver les cellules épithéliales du limbe in vitro sur un gel de fibrine qui sera greffé dans l’œil des patients. L’étude permettra d'effectuer la greffe des 5 derniers patients, de finaliser le suivi de 1 an de tous les patients, d’effectuer les analyses des résultats et de la faisabilité d’utiliser les CECA pour les indications proposées. Notre équipe multidisciplinaire permettra la translation clinique du produit du génie tissulaire: CECA. Nous serons les premiers au Canada à offrir ce traitement qui vise à améliorer la vision des patients. |
01/12/2016 |
31/12/2017 |
| 2016 |
James Johnson (P) |
University of British Columbia |
Recherche d’impact, clinical translation |
Johnson |
Chercheur principal |
James Johnson |
100 000 |
Image-based screening to enhance insulin production in human embryonic stem cells |
Diabète |
|
Diabetes is caused by the lack of insulin secreting β-cells. A major goal of regenerative
medicine is the generation of fully functional β-cells, either from stem cells, but this goal has not
yet been achieved despite optimistic press reports. The path to the clinic is clear, with the first
clinical trial of transplantation of progenitor cells into patients currently underway in the US and
Canada led by the US-based Viacyte. This company hopes that these progenitor cells will
mature into fully functional β-cells after transplantation, but it is not clear from interim reports
whether this occurs in humans. Thus, efforts to generate and transplant more mature cells are
likely to be the focus of the field over the next few years. With SCN support, our laboratory
published the first, and still only, multi-parameter kinetic high-throughput screening focused on
β-cell survival and differentiation. Hits from these robust screens were subsequently validated in
human cells and in animal models. Here, we will apply our tools to embryonic stem cells and
partner with the CDRD to expand the screening up to libraries with 250K compounds. The
identification of drugs that can increase insulin production in stem cells would be a major
breakthrough. |
01/12/2016 |
31/12/2017 |
| 2016 |
Timothy Kieffer (P) |
University of British Columbia |
Recherche d’impact, clinical translation |
Kieffer |
Chercheur principal |
Timothy Kieffer |
100 000 |
Biodistribution of differentiated stem cells following subcutaneous transplant |
Diabète |
|
Diabetes is a disease caused by insufficient production of the hormone insulin, resulting in elevated blood sugar levels and damage to several tissues leading to debilitating complications. Our overall goal is to develop a cell-based therapy for diabetes. We believe this can be achieved by the transplant of differentiated stem cells under the skin, whereby the cells take over the automatic production of insulin and control of blood sugar levels. We have developed cell culture procedures to generate large quantities of insulin-producing cells that can reverse diabetes in rodents. With support from JDRF, we are examining the effectiveness of this approach when transplanting the cells under the skin. We now plan to extend these studies by including genetically modified stem cells that will enable us to non-invasively image the cells following transplant in order to monitor their distribution throughout the body to confirm if the cells remain at the site of transplant. In addition, we will test a novel ‘kill-switch’ to determine if we can eliminate the transplanted cells by treatment with an otherwise harmless inducing agent. Collectively, these studies may provide important knowledge and added levels of safety to justify trying this therapeutic approach in humans with diabetes. |
01/12/2016 |
31/12/2017 |
| 2016 |
Megan Levings (P) |
University of British Columbia |
Recherche d’impact, clinical translation |
Levings |
Chercheur principal |
Megan Levings, Lori West |
62 667 |
Garbage to Gold: Expansion of therapeutics regulatory T cells from discarded thymus |
Sang; leucémie |
|
For many patients with blood cancers, the only option for cure is hematopoietic stem cell transplantation (HSCT). Unfortunately, HSCT can cause a complication called graft-versus-host disease (GVHD), which happens when donor immune cells attack the patient’s healthy tissues. HSCT would be safer if we could prevent/reduce GVHD without affecting its anti-cancer action.
We are developing a novel cellular therapy with regulatory T cells (Treg) to use in combination with HSCT to prevent or treat GVHD. Early studies show promise, but using currently available protocols it is difficult and time-consuming to obtain enough Tregs with the correct properties.
We investigated the possibility of isolating Tregs from a new source: a gland called the thymus, which is discarded in children undergoing heart surgery. We found huge numbers of Tregs in the thymus and that thymic Tregs prevent GVHD in mice. In order to test thymic Tregs in a clinical trial in humans we now need to develop optimized and standard methods for large-scale expansion of thymic Tregs. We will work with STEMCELL Technologies to create new reagents and protocols to achieve this aim. This ground-work will be a key step in translating this approach to the bedside to test if delivering thymic Tregs can reduce GVHD. |
01/12/2016 |
31/12/2017 |
| 2016 |
Lori West (C) |
University of Alberta |
Recherche d’impact, clinical translation |
Levings |
Cochercheur |
Megan Levings, Lori West |
37 333 |
Garbage to Gold: Expansion of therapeutics regulatory T cells from discarded thymus |
Sang; leucémie |
|
For many patients with blood cancers, the only option for cure is hematopoietic stem cell transplantation (HSCT). Unfortunately, HSCT can cause a complication called graft-versus-host disease (GVHD), which happens when donor immune cells attack the patient’s healthy tissues. HSCT would be safer if we could prevent/reduce GVHD without affecting its anti-cancer action.
We are developing a novel cellular therapy with regulatory T cells (Treg) to use in combination with HSCT to prevent or treat GVHD. Early studies show promise, but using currently available protocols it is difficult and time-consuming to obtain enough Tregs with the correct properties.
We investigated the possibility of isolating Tregs from a new source: a gland called the thymus, which is discarded in children undergoing heart surgery. We found huge numbers of Tregs in the thymus and that thymic Tregs prevent GVHD in mice. In order to test thymic Tregs in a clinical trial in humans we now need to develop optimized and standard methods for large-scale expansion of thymic Tregs. We will work with STEMCELL Technologies to create new reagents and protocols to achieve this aim. This ground-work will be a key step in translating this approach to the bedside to test if delivering thymic Tregs can reduce GVHD. |
01/12/2016 |
31/12/2017 |
| 2016 |
Kelly McNagny (P) |
University of British Columbia |
Recherche d’impact, clinical translation |
McNagny |
Chercheur principal |
Kelly McNagny |
100 000 |
CAR-T cell therapy targeting tumor-specific modifications of Podocalyxin in triple negative breast cancer |
Cancer du sein |
|
Despite being more likely to receive chemotherapy, or surgery plus chemotherapy, the 5-year survival of triple-negative breast cancer (TNBC) patients remains below 65%1, and novel targeted approaches are urgently needed. Chimeric antigen receptors (CAR) combine the Fv portion of monoclonal antibodies (as a single chain Fv; scFv) and the intracellular signaling domain of immune co-stimulatory molecules and the CD3 molecule with the goal of activating T-cells in an antigen-specific manner, independent of their endogenous T cell receptor (TCR) repertoire2. CAR-T therapies targeting the surface molecule CD19 have shown exceptional promise in a limited number of clinical trials for B cell malignancies3, 4. Unfortunately, there are no obvious targets on the surface of TNBC cells that could be amenable to targeting by CAR-T cells. Previous work funded by the SCN demonstrated that the protein, Podocalyxin (Podxl) could be targeted by a naked antibody to reduce invasion and metastasis of TNBC cells in vivo, and that Podxl regulates their clonogenic potential (“stemness”) in vitro. Herein we propose to develop a novel humanized antibody (hPodo447) that recognizes a post-translational modification of Podxl found on TNBC cells (and a range of other tumors) as a targeting arm for CAR-T cell therapy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Paula Foster (C) |
University of Western Ontario |
Recherche d’impact, clinical translation |
Viswanathan |
Cochercheur |
Sowmya Viswanathan, Mohit Kapoor, Paula Foster |
47 000 |
Iron labeled-mesenchymal stromal cells for clinical tracking in amended Phase I trial in osteoarthritis patients |
Ostéoarthrite, ostéo-arthrite |
|
We have commenced a dose finding study using autologous mesenchymal stromal cells (MSCs) in Osteoarthritis (OA) patients, but have not identified an efficacious dose to date. To proceed further with a Phase II trial using allogenic MSCs, we need to identify a safe and efficacious MSC dose. Labeling MSCs with a Health Canada approved iron nanoparticle, Feraheme® (approved for anemia) will allow us to track persistence and localization of MSCs injected locally into the knee of OA patients, and will provide the necessary information to better determine dosing, frequency and use of carriers in the future. We propose to complete a study with sufficient animals to evaluate safety and efficacy of iron-labeled mouse MSCs. Iron and fluorescent-labeled MSCs are injected into the knee joints of mice, which have undergone a surgical injury to their meniscus to initiate arthritic inflammatory and degradation processes. Cells are tracked by magnetic resonance imaging (MRI) and confirmed by histology at the time of sacrifice; importantly, histology in other organs and blood chemistry tests will confirm safety of using iron-labeled MSCs. A pre-clinical trial consultation (CTA) with Health Canada confirmed their support for this experimental approach as the basis for initiating trials using iron-labeled MSCs. |
01/12/2016 |
31/12/2017 |
| 2016 |
Mohit Kapoor (C) |
University Health Network |
Recherche d’impact, clinical translation |
Viswanathan |
Cochercheur |
Sowmya Viswanathan, Mohit Kapoor, Paula Foster |
5 000 |
Iron labeled-mesenchymal stromal cells for clinical tracking in amended Phase I trial in osteoarthritis patients |
Ostéoarthrite, ostéo-arthrite |
|
We have commenced a dose finding study using autologous mesenchymal stromal cells (MSCs) in Osteoarthritis (OA) patients, but have not identified an efficacious dose to date. To proceed further with a Phase II trial using allogenic MSCs, we need to identify a safe and efficacious MSC dose. Labeling MSCs with a Health Canada approved iron nanoparticle, Feraheme® (approved for anemia) will allow us to track persistence and localization of MSCs injected locally into the knee of OA patients, and will provide the necessary information to better determine dosing, frequency and use of carriers in the future. We propose to complete a study with sufficient animals to evaluate safety and efficacy of iron-labeled mouse MSCs. Iron and fluorescent-labeled MSCs are injected into the knee joints of mice, which have undergone a surgical injury to their meniscus to initiate arthritic inflammatory and degradation processes. Cells are tracked by magnetic resonance imaging (MRI) and confirmed by histology at the time of sacrifice; importantly, histology in other organs and blood chemistry tests will confirm safety of using iron-labeled MSCs. A pre-clinical trial consultation (CTA) with Health Canada confirmed their support for this experimental approach as the basis for initiating trials using iron-labeled MSCs. |
01/12/2016 |
31/12/2017 |
| 2016 |
Sowmya Viswanathan (P) |
University Health Network |
Recherche d’impact, clinical translation |
Viswanathan |
Chercheur principal |
Sowmya Viswanathan, Mohit Kapoor, Paula Foster |
48 000 |
Iron labeled-mesenchymal stromal cells for clinical tracking in amended Phase I trial in osteoarthritis patients |
Ostéoarthrite, ostéo-arthrite |
|
We have commenced a dose finding study using autologous mesenchymal stromal cells (MSCs) in Osteoarthritis (OA) patients, but have not identified an efficacious dose to date. To proceed further with a Phase II trial using allogenic MSCs, we need to identify a safe and efficacious MSC dose. Labeling MSCs with a Health Canada approved iron nanoparticle, Feraheme® (approved for anemia) will allow us to track persistence and localization of MSCs injected locally into the knee of OA patients, and will provide the necessary information to better determine dosing, frequency and use of carriers in the future. We propose to complete a study with sufficient animals to evaluate safety and efficacy of iron-labeled mouse MSCs. Iron and fluorescent-labeled MSCs are injected into the knee joints of mice, which have undergone a surgical injury to their meniscus to initiate arthritic inflammatory and degradation processes. Cells are tracked by magnetic resonance imaging (MRI) and confirmed by histology at the time of sacrifice; importantly, histology in other organs and blood chemistry tests will confirm safety of using iron-labeled MSCs. A pre-clinical trial consultation (CTA) with Health Canada confirmed their support for this experimental approach as the basis for initiating trials using iron-labeled MSCs. |
01/12/2016 |
31/12/2017 |
| 2016 |
Guy Sauvageau (C) |
Université de Montréal |
Recherche d’impact, clinical translation |
Zandstra |
Cochercheur |
Peter Zandstra, Julie Audet, Guy Sauvageau |
40 000 |
Clinical culture optimization to maximize cord blood derived hematopoietic stem cell expansion |
Sang |
|
We have developed a first-in-class umbilical cord blood (UCB)-derived hematopoietic stem cell (HSC) expansion platform that combines a “fed-batch” (FB) bioprocess with the HSC-stimulating small molecule UM171. This process is in a Phase 1-2 clinical trial. Our next step is to enhance the clinical efficacy and commercial potential of the grafts produced from the FB + UM171 bioprocess by reducing production costs and increasing HSC expansion outputs. We propose to accomplish this by optimizing medium additives such as cytokines and novel proprietary molecules using powerful statistical design strategies. Cell output will be assessed by flow cytometry analysis for HSC-associated phenotypes (CD34+CD45RA-CD90+CD201-) and functional cell engraftment in immunocompromised mice. We anticipate that this medium optimization process will double our HSC output in shorter culture periods (culture time recently shortened from 12 to 7 days), thereby reducing our cost-of-goods to less than $5000 per patient. This goal would give our Canadian Biotech partner, ExCellThera, a dramatic advantage over our international competitors who typically perform cultures over several weeks at a cost-per-culture exceeding $40,000. At the end of our 1 year funding period the conditions established in this study will be incorporated into the Phase 1-2 clinical trial for the use of expanded HSCs to treat leukemia. |
01/12/2016 |
31/12/2017 |
| 2016 |
Julie Audet (C) |
University of Toronto |
Recherche d’impact, clinical translation |
Zandstra |
Cochercheur |
Peter Zandstra, Julie Audet, Guy Sauvageau |
10 000 |
Clinical culture optimization to maximize cord blood derived hematopoietic stem cell expansion |
Sang |
|
We have developed a first-in-class umbilical cord blood (UCB)-derived hematopoietic stem cell (HSC) expansion platform that combines a “fed-batch” (FB) bioprocess with the HSC-stimulating small molecule UM171. This process is in a Phase 1-2 clinical trial. Our next step is to enhance the clinical efficacy and commercial potential of the grafts produced from the FB + UM171 bioprocess by reducing production costs and increasing HSC expansion outputs. We propose to accomplish this by optimizing medium additives such as cytokines and novel proprietary molecules using powerful statistical design strategies. Cell output will be assessed by flow cytometry analysis for HSC-associated phenotypes (CD34+CD45RA-CD90+CD201-) and functional cell engraftment in immunocompromised mice. We anticipate that this medium optimization process will double our HSC output in shorter culture periods (culture time recently shortened from 12 to 7 days), thereby reducing our cost-of-goods to less than $5000 per patient. This goal would give our Canadian Biotech partner, ExCellThera, a dramatic advantage over our international competitors who typically perform cultures over several weeks at a cost-per-culture exceeding $40,000. At the end of our 1 year funding period the conditions established in this study will be incorporated into the Phase 1-2 clinical trial for the use of expanded HSCs to treat leukemia. |
01/12/2016 |
31/12/2017 |
| 2016 |
Peter Zandstra (P) |
University of Toronto |
Recherche d’impact, clinical translation |
Zandstra |
Chercheur principal |
Peter Zandstra, Julie Audet, Guy Sauvageau |
50 000 |
Clinical culture optimization to maximize cord blood derived hematopoietic stem cell expansion |
Sang |
|
We have developed a first-in-class umbilical cord blood (UCB)-derived hematopoietic stem cell (HSC) expansion platform that combines a “fed-batch” (FB) bioprocess with the HSC-stimulating small molecule UM171. This process is in a Phase 1-2 clinical trial. Our next step is to enhance the clinical efficacy and commercial potential of the grafts produced from the FB + UM171 bioprocess by reducing production costs and increasing HSC expansion outputs. We propose to accomplish this by optimizing medium additives such as cytokines and novel proprietary molecules using powerful statistical design strategies. Cell output will be assessed by flow cytometry analysis for HSC-associated phenotypes (CD34+CD45RA-CD90+CD201-) and functional cell engraftment in immunocompromised mice. We anticipate that this medium optimization process will double our HSC output in shorter culture periods (culture time recently shortened from 12 to 7 days), thereby reducing our cost-of-goods to less than $5000 per patient. This goal would give our Canadian Biotech partner, ExCellThera, a dramatic advantage over our international competitors who typically perform cultures over several weeks at a cost-per-culture exceeding $40,000. At the end of our 1 year funding period the conditions established in this study will be incorporated into the Phase 1-2 clinical trial for the use of expanded HSCs to treat leukemia. |
01/12/2016 |
31/12/2017 |
| 2016 |
Kristin Hope (P) |
McMaster University |
Recherche d’impact, commercialisation |
Hope |
Chercheur principal |
Kristin Hope |
100 000 |
Methods and compositions for expansion of human hematopoietic stem and progenitor cells |
Sang |
|
|
01/12/2016 |
31/12/2017 |
| 2016 |
Joanne Matsubara (P) |
University of British Columbia |
Recherche d’impact, commercialisation |
Matsubara |
Chercheur principal |
Joanne Matsubara, Marinko Sarunic |
85 502 |
Treating advanced retinal degeneration - rebuilding multiple co-dependent retinal layers with a single injection of stem cell-derived graft |
Oculaire |
|
|
01/12/2016 |
31/12/2017 |
| 2016 |
Marinko Sarunic (C) |
Simon Fraser University |
Recherche d’impact, commercialisation |
Matsubara |
Cochercheur |
Joanne Matsubara, Marinko Sarunic |
14 000 |
Treating advanced retinal degeneration - rebuilding multiple co-dependent retinal layers with a single injection of stem cell-derived graft |
Oculaire |
|
|
01/12/2016 |
31/12/2017 |
| 2016 |
Ian Rogers (P) |
Sinai Health System |
Recherche d’impact, commercialisation |
Rogers |
Chercheur principal |
Ian Rogers |
90 811 |
Improving efficacy and economics of kidney disease therapies using iPS cells |
Néphropathie, maladie du rein |
|
|
01/12/2016 |
31/12/2017 |
| 2016 |
Mark Ungrin (P) |
University of Calgary |
Recherche d’impact, commercialisation |
Ungrin |
Chercheur principal |
Mark Ungrin |
100 000 |
Scalable production of engineered microtissues |
Fabrication |
|
|
01/12/2016 |
31/12/2017 |
| 2016 |
Stephanie Willerth (P) |
University of Victoria |
Recherche d’impact, commercialisation |
Willerth |
Chercheur principal |
Stephanie Willerth |
100 000 |
3D bioprinting of neural tissue from human pluripotent stem cells |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
|
01/12/2016 |
31/12/2017 |
| 2016 |
Jing Wang (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 554 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Paul Frankland (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 554 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
David Kaplan (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Ann Yeh (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Douglas Munoz (C) |
Queen's University |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Donald Mabbott (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Freda Miller (P) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Chercheur principal |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Cindi Morshead (C) |
University of Toronto |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales; sclérose en plaques |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Wolfram Tetzlaff (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Wolfram Tetzlaff, Jing Wang, Cindi Morshead, Donald Mabbott, Douglas Munoz, Ann Yeh, David Kaplan, Paul Frankland |
55 556 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter, which contains myelinated axons, occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident neural precursor cells (NPCs) that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous NPCs to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from NPCs and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic, with the ultimate goal of a clinical trial for metformin in children and adolescents with white matter damage. To attain this goal, we will perform preclinical work in different mouse models of white matter damage, asking whether metformin can enhance brain function as it promotes white matter repair. At the same time, we will develop outcome measures that will allow us to measure the efficacy of metformin in children and adolescents with white matter damage. Finally, we will search for additional methods of activating brain stem cells so that they make more oligodendrocytes, with the idea that ultimately we will use combinatorial approaches to treat white matter damage in humans. To pursue these objectives, we have assembled an expert team including both basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). If we obtain positive results in our clinical trial, then this will lead to a dramatic shift in how we treat children/teenagers with white matter injury. In addition, this work will pave the way for future additional clinical trials in children and adults with white matter damage as a consequence of multiple sclerosis, stroke, traumatic brain injury, spinal cord injury and cerebral palsy. |
01/12/2016 |
31/12/2017 |
| 2016 |
Guy Sauvageau (C) |
Université de Montréal |
Équipes de recherche sur les maladies |
Marinier |
Cochercheur |
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau |
49 992 |
Development of hematopoietic stem cell expanding molecules towards the ideal transplant |
Sang |
|
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications. |
01/12/2016 |
31/12/2017 |
| 2016 |
Anne Marinier (P) |
Université de Montréal |
Équipes de recherche sur les maladies |
Marinier |
Chercheur principal |
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau |
405 557 |
Development of hematopoietic stem cell expanding molecules towards the ideal transplant |
Sang |
|
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications. |
01/12/2016 |
31/12/2017 |
| 2016 |
Connie Eaves (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Marinier |
Cochercheur |
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau |
30 750 |
Development of hematopoietic stem cell expanding molecules towards the ideal transplant |
Sang |
|
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications. |
01/12/2016 |
31/12/2017 |
| 2016 |
Keith Humphries (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Marinier |
Cochercheur |
Anne Marinier, Keith Humphries, James Shapiro, Connie Eaves, Guy Sauvageau |
13 700 |
Development of hematopoietic stem cell expanding molecules towards the ideal transplant |
Sang |
|
Hematopoietic stem cell (HSC) transplantation (HSCT) is based on the transfer of HSCs from donors’ mobilized peripheral blood or bone marrow to recipients. As HLA matching is critical for HSCT and 30% of patients lack an HLA identical donor, cord blood (CB) is used as an alternative source of HSCs. Despite major assets associated with CB transplants, such as the high efficacy of anti-disease (leukemia, lymphoma) effect and low incidence of chronic graft versus host disease, the low cell dose in CB units linked to high transplant related mortality precludes their widespread use.
With the general objective of developing the best protocol for HSCT, we searched for strategies aimed at expanding CB HSCs and discovered the molecule UM171, which uniquely provided expanded CB units that are currently tested in a Phase I/II clinical trial. Although significantly improved after UM171 treatment, small CB grafts would benefit from the effect of an additional molecule that further expands stem and progenitor cells. To that end, we recently identified UM092, for which initial structure-activity relationship (SAR) studies demonstrated a potential for further structural optimization, an activity proposed in this agreement. Following pre-clinical development activities with the optimised analog including in vivo pharmacokinetics and toxicity evaluation, the GMP production of the molecule will then be undertaken, delivering material ready for extended phase II clinical studies.
Based on our experience in developing UM171, a Canadian team consisting of chemists with strong industrial expertise and renowned stem cell biologists was assembled to efficiently develop SAR and identify the best complements to UM171. Experts in drug metabolism/pharmacokinetics and toxicology have also joined the team for characterization of the new molecules and the expanded cellular material, along with cell therapy specialists to deliver the final expanded cell product. Supported by committed partners such as ExcellThera, to which the optimised UM092 will be out-licensed for the development of our novel HSCT technology, StemCell Technologies, as the likely commercial supplier of the novel compounds for research, Hôpital Charles-Le-Moyne, for CBs supplying, and various funding agencies, this team is in a strong position to advance to clinical studies this transformative technology that will increase CB accessibility to a larger number of patients from Canada and abroad once on the market. This will undoubtedly lead to a paradigm shift in the field of HSCT with CB emerging as the best HSC source for the treatment of hematologic malignancies as well as non-oncology indications. |
01/12/2016 |
31/12/2017 |
| 2016 |
Timothy Kieffer (P) |
University of British Columbia |
Équipes de recherche sur les maladies |
Kieffer |
Chercheur principal |
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman |
125 000 |
Optimizing stem cell derived beta-cell therapy for diabetes |
Diabète |
|
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment. |
01/12/2016 |
31/12/2017 |
| 2016 |
James Johnson (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Kieffer |
Cochercheur |
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman |
125 000 |
Optimizing stem cell derived beta-cell therapy for diabetes |
Diabète |
|
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment. |
01/12/2016 |
31/12/2017 |
| 2016 |
Francis Lynn (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Kieffer |
Cochercheur |
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman |
125 000 |
Optimizing stem cell derived beta-cell therapy for diabetes |
Diabète |
|
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment. |
01/12/2016 |
31/12/2017 |
| 2016 |
Brad Hoffman (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Kieffer |
Cochercheur |
Timothy Kieffer, James Johnson, Bruce Verchere, Francis Lynn, Brad Hoffman |
125 000 |
Optimizing stem cell derived beta-cell therapy for diabetes |
Diabète |
|
Diabetes, or high blood sugar, results from a deficit in the function of a small population of highly specialized cells in the pancreas, called -cells, that produce the hormone insulin. Fortunately, the Canadian discovery of insulin allows patients with diabetes to survive by daily injections. Despite this, patients still suffer from debilitating complications that significantly impact quality of life and reduce lifespan due to imprecise regulation of blood sugar levels. Canadians demonstrated that transplant of -cells obtained from organ donors can completely eliminate the need for insulin injections. However, this procedure is limited to less than 1% of the millions who suffer from diabetes because of a shortage of organ donors.
Laboratories around the world have made significant strides towards producing unlimited quantities of -like cells from stem cells. One company has even started clinical trials, transplanting cells derived from stem cells into more than a dozen diabetic patients thus far. While this is significant and encouraging progress, unanswered questions prevent us from cultivating fully functional -cells. The goal of our research program is to identify why our current protocols fail to generate functional -cells and to develop ways to surmount this barrier to enable the potential cure for diabetes. These cells will also be useful in researching how diabetes occurs, which could lead to new ways of preventing the disease.
Team leader Dr. Kieffer has worked closely with industry collaborators to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards -cells. He has been joined in these efforts by Dr. Johnson, a leading authority on the pathways that define mature -cells and sophisticated imaging techniques. Dr. Lynn is also an expert in stem cell culture and studies how -cells develop and mature in the body, which will be critical knowledge for duplicating this process in the laboratory. Dr. Hoffman studies the complex genetic interactions that orchestrate -cell development and uses powerful sequencing techniques to ‘fingerprint’ the genetic code of mature -cells and those generated in our laboratories. Both functional and gene analysis technologies will be critical to pinpoint deficits in currently produced cells, and also to validate when we successfully produce mature -cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature -cells for what promises to be a new paradigm in diabetes treatment. |
01/12/2016 |
31/12/2017 |
| 2016 |
Bruce Verchere (P) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Chercheur principal |
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings |
200 000 |
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/12/2016 |
31/12/2017 |
| 2016 |
Francis Lynn (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings |
160 000 |
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/12/2016 |
31/12/2017 |
| 2016 |
Timothy Kieffer (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings |
65 000 |
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/12/2016 |
31/12/2017 |
| 2016 |
Megan Levings (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Guy Sauvageau, Timothy Kieffer, Megan Levings |
65 000 |
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/12/2016 |
31/12/2017 |
| 2016 |
Armand Keating (C) |
University Health Network |
Équipes de recherche sur les maladies |
Nagy |
Cochercheur |
Andras Nagy, Armand Keating, Timothy Kieffer, Mohit Kapoor |
83 585 |
Combining gene and mesenchymal stromal cell therapies: steps towards curing arthritis |
Ostéoarthrite, ostéo-arthrite |
|
Osteoarthritis (OA) is a debilitating disease characterized by progressive articular cartilage degeneration and is commonly followed by subchondral bone destruction and synovial inflammation. Globally, OA is the most common musculoskeletal disease, and more than three million Canadians have a reduced quality life because of it. With an aging population, there is a glaring need for safe and effective treatments for this debilitating chronic condition.
The current management of OA is mostly palliative and aimed at controlling pain and improving diseased joint function with physical therapy, while taking acetaminophen or non-steroidal systemic anti-inflammatories. Although these treatments reduce pain in some people, they do not cure the disease or prevent articular cartilage degeneration and disease progression. In an effort to reduce cartilage destruction in OA, some researchers have begun targeting inflammatory mediators, like (TNFα, IL-1B), that regulate the pain response as well as cartilage degeneration. Moreover, Mesenchymal Stromal Cells (MSCs), which can be isolated from various adult and neonatal tissues, and derivatives of pluripotent stem cells, have immunomodulatory properties that make them prime candidates for cell therapies to treat inflammatory diseases such as OA. An ongoing Health Canada approved phase I/II dose-escalation safety and efficacy study at the Toronto Western Hospital by members of this team is investigating the consequence of autologous injection of MSCs into the knee joints of patients with OA.
Here, we propose a novel approach by combining gene and cell therapy for the treatment of OA. We will harness mesenchymal stromal-like cells and chondrocytes, derived from pluripotent cells, to mediate an optimized anti-inflammatory response, while drug-inducibly delivering local-acting IL-1BRII, membrane-bound TGF-β1, a novel VEGF sticky-trap and TNFα sticky-trap biologics via transplanted cells to diseased joints. Prior to transplantation, the source of the therapeutic cells will be additionally modified to render them both non-tumorigenic (“Fail-Safe”) and immunologically tolerated (“cloaked”).
Our team combines decades of expertise in stem cell manipulation, the development of targeted biologics (Nagy), preclinical models to study and treat OA (Kapoor), MSC biology (Keating), and clinical use of MSCs to investigate novel disease treatments (Keating, Viswanathan). Combining gene and stem cell therapies is expected to increase the efficacy of treatment for this urgent clinical need. In cooperation with the CCRM, our approach is already on the path to commercialization and translation with the incorporation of a spin-off company (panCELLa Inc.), whose business plan is built on the clinical application of the “fail-safe” cell technology. |
01/12/2016 |
31/12/2017 |
| 2016 |
Mohit Kapoor (C) |
University Health Network |
Équipes de recherche sur les maladies |
Nagy |
Cochercheur |
Andras Nagy, Armand Keating, Timothy Kieffer, Mohit Kapoor |
132 046 |
Combining gene and mesenchymal stromal cell therapies: steps towards curing arthritis |
Ostéoarthrite, ostéo-arthrite |
|
Osteoarthritis (OA) is a debilitating disease characterized by progressive articular cartilage degeneration and is commonly followed by subchondral bone destruction and synovial inflammation. Globally, OA is the most common musculoskeletal disease, and more than three million Canadians have a reduced quality life because of it. With an aging population, there is a glaring need for safe and effective treatments for this debilitating chronic condition.
The current management of OA is mostly palliative and aimed at controlling pain and improving diseased joint function with physical therapy, while taking acetaminophen or non-steroidal systemic anti-inflammatories. Although these treatments reduce pain in some people, they do not cure the disease or prevent articular cartilage degeneration and disease progression. In an effort to reduce cartilage destruction in OA, some researchers have begun targeting inflammatory mediators, like (TNFα, IL-1B), that regulate the pain response as well as cartilage degeneration. Moreover, Mesenchymal Stromal Cells (MSCs), which can be isolated from various adult and neonatal tissues, and derivatives of pluripotent stem cells, have immunomodulatory properties that make them prime candidates for cell therapies to treat inflammatory diseases such as OA. An ongoing Health Canada approved phase I/II dose-escalation safety and efficacy study at the Toronto Western Hospital by members of this team is investigating the consequence of autologous injection of MSCs into the knee joints of patients with OA.
Here, we propose a novel approach by combining gene and cell therapy for the treatment of OA. We will harness mesenchymal stromal-like cells and chondrocytes, derived from pluripotent cells, to mediate an optimized anti-inflammatory response, while drug-inducibly delivering local-acting IL-1BRII, membrane-bound TGF-β1, a novel VEGF sticky-trap and TNFα sticky-trap biologics via transplanted cells to diseased joints. Prior to transplantation, the source of the therapeutic cells will be additionally modified to render them both non-tumorigenic (“Fail-Safe”) and immunologically tolerated (“cloaked”).
Our team combines decades of expertise in stem cell manipulation, the development of targeted biologics (Nagy), preclinical models to study and treat OA (Kapoor), MSC biology (Keating), and clinical use of MSCs to investigate novel disease treatments (Keating, Viswanathan). Combining gene and stem cell therapies is expected to increase the efficacy of treatment for this urgent clinical need. In cooperation with the CCRM, our approach is already on the path to commercialization and translation with the incorporation of a spin-off company (panCELLa Inc.), whose business plan is built on the clinical application of the “fail-safe” cell technology. |
01/12/2016 |
31/12/2017 |
| 2016 |
Andras Nagy (P) |
Sinai Health System |
Équipes de recherche sur les maladies |
Nagy |
Chercheur principal |
Andras Nagy, Armand Keating, Timothy Kieffer, Mohit Kapoor |
178 992 |
Combining gene and mesenchymal stromal cell therapies: steps towards curing arthritis |
Ostéoarthrite, ostéo-arthriteOstéoarthrite; ostéo-arthrite |
|
Osteoarthritis (OA) is a debilitating disease characterized by progressive articular cartilage degeneration and is commonly followed by subchondral bone destruction and synovial inflammation. Globally, OA is the most common musculoskeletal disease, and more than three million Canadians have a reduced quality life because of it. With an aging population, there is a glaring need for safe and effective treatments for this debilitating chronic condition.
The current management of OA is mostly palliative and aimed at controlling pain and improving diseased joint function with physical therapy, while taking acetaminophen or non-steroidal systemic anti-inflammatories. Although these treatments reduce pain in some people, they do not cure the disease or prevent articular cartilage degeneration and disease progression. In an effort to reduce cartilage destruction in OA, some researchers have begun targeting inflammatory mediators, like (TNFα, IL-1B), that regulate the pain response as well as cartilage degeneration. Moreover, Mesenchymal Stromal Cells (MSCs), which can be isolated from various adult and neonatal tissues, and derivatives of pluripotent stem cells, have immunomodulatory properties that make them prime candidates for cell therapies to treat inflammatory diseases such as OA. An ongoing Health Canada approved phase I/II dose-escalation safety and efficacy study at the Toronto Western Hospital by members of this team is investigating the consequence of autologous injection of MSCs into the knee joints of patients with OA.
Here, we propose a novel approach by combining gene and cell therapy for the treatment of OA. We will harness mesenchymal stromal-like cells and chondrocytes, derived from pluripotent cells, to mediate an optimized anti-inflammatory response, while drug-inducibly delivering local-acting IL-1BRII, membrane-bound TGF-β1, a novel VEGF sticky-trap and TNFα sticky-trap biologics via transplanted cells to diseased joints. Prior to transplantation, the source of the therapeutic cells will be additionally modified to render them both non-tumorigenic (“Fail-Safe”) and immunologically tolerated (“cloaked”).
Our team combines decades of expertise in stem cell manipulation, the development of targeted biologics (Nagy), preclinical models to study and treat OA (Kapoor), MSC biology (Keating), and clinical use of MSCs to investigate novel disease treatments (Keating, Viswanathan). Combining gene and stem cell therapies is expected to increase the efficacy of treatment for this urgent clinical need. In cooperation with the CCRM, our approach is already on the path to commercialization and translation with the incorporation of a spin-off company (panCELLa Inc.), whose business plan is built on the clinical application of the “fail-safe” cell technology. |
01/12/2016 |
31/12/2017 |
| 2016 |
Gregory Korbutt (C) |
University of Alberta |
Équipes de recherche sur les maladies |
Shapiro |
Cochercheur |
James Shapiro, Gregory Korbutt |
244 905 |
Development of a novel stem cell-derived transplant modality for type 1 diabetes |
Diabète |
|
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/12/2016 |
31/12/2017 |
| 2016 |
James Shapiro (P) |
University of Alberta |
Équipes de recherche sur les maladies |
Shapiro |
Chercheur principal |
James Shapiro, Gregory Korbutt |
252 000 |
Development of a novel stem cell-derived transplant modality for type 1 diabetes |
Diabète |
|
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/12/2016 |
31/12/2017 |
| 2016 |
Vahab Soleimani (P) |
Jewish General Hospital |
Équipes de recherche sur les maladies |
Soleimani |
Chercheur principal |
Vahab Soleimani |
200 000 |
Interfering niche-related reprogramming of stem cells during aging |
Muscle, muscles |
|
Adult stem cells are indispensable for tissue homeostasis and repair. In the musculoskeletal system (i.e. skeletal muscle, bone and connective tissue), there is a severe age-related decline in stem cell functionality and tissue repair. This functional decline of stem cells leads to degenerative diseases such as osteoporosis and sarcopenia in the elderly population. Recent experimental evidence suggests that age-related defect in tissue repair could be reversed. However, the molecular mechanisms underlying the plasticity and reversibility of tissue repair in degenerative diseases such as sarcopenia and osteoporosis remains a challenge. Multiple lines of evidence suggest that epigenetic alterations play key roles in the aging process, as cells from aged individuals exhibit reduced area of heterochromatin and loss of repressive histone marks. The reversibility of epigenetic mechanisms by various drugs provides great opportunities to develop urgently needed therapies for many debilitating diseases including the age-related musculoskeletal disorders. However, there is a knowledge gap on how stem cell functionality is lost in degenerative disorders and how aging in general impacts stem cell function and tissue repair. Adult stem cells reside within a defined anatomical location called “the niche” where the stem cell constantly communicates with the surrounding environment and with the neighbouring cells. In patients with degenerative diseases and during aging the environment surrounding the stem cells changes with regards to the cellular content and the chemical signals. Consequently, in the diseased conditions stem cells lose their ability to maintain tissue repair. In this project we aim to determine how changes in the stem cell niche during aging impairs tissue regeneration using hematopoietic, mesenchymal and skeletal muscle stem cells. We hypothesize that the diseased niche alters gene expression profile by modifying the stem cell epigenome. Therefore, we will perform allogeneic stem cell transplantation between young and old mice and map the transcriptional and epigenetic changes that take place as a result of changing niche environment. Using stem cells from three distinct lineages will identify conserved genetic networks that are altered with age. Importantly, by doing reciprocal stem cell transplantation from young to old and vice versa we will determine the “reversible” genetic networks that can be targeted in degenerative musculoskeletal diseases. Finally, we will validate the results in human cells and tissue biopsies to assess the translational potentials. The long-term goal of this project is to develop novel stem cell-based therapies to boost tissue regeneration for musculoskeletal degenerative disorders. |
01/12/2016 |
31/12/2017 |
| 2016 |
Massimiliano Paganelli (P) |
CHU Sainte-Justine |
Équipes de recherche sur les maladies |
Paganelli |
Chercheur principal |
Massimiliano Paganelli |
199 982 |
Treatment of chronic liver failure by stem cell-derived mature liver tissue |
Insuffisance hépatique |
|
One in ten Canadians is affected by liver disease. The standard of care for liver failure (the common outcome of any progressive liver disease) is liver transplantation, but only 400 transplants are performed each year in Canada for over 5000 liver deaths/year. Thus, there is an urgent need for new therapies capable of replacing liver functions in children and adults with cirrhosis and liver failure. The final aim of this multidisciplinary project is to develop and test an innovative stem cell-based product to restore the lacking liver functions in such patients, improving survival and preventing/treating complications. Our team is composed of a transplant hepatologist expert in stem cell therapy (Dr. Paganelli, CHU Sainte-Justine), two leaders in the field of biomaterials (Dr. Shikanov at University of Michigan, and Dr. Ma, Cornell University), and a molecular oncologist expert in pre-clinical studies (Dr. Petrocca, Boston University). Using our clinical-grade human stem cells we are able to generate 3D cellular microaggregates (organoids) expressing the functions of a healthy liver. We will embed such organoids in a Health Canada-approved synthetic hydrogel we previously developed. Such a biomaterial supports the survival and maturation of the embedded organoids, allowing them to exchange nutrients and substances with the environment and providing complete isolation from the immune system upon implantation into a recipient. Upon encapsulation into this semi-solid hydrogel, our organoids will express most of the functions of a mature liver tissue. Once implanted into a patient with liver failure, such an encapsulated mature liver tissue (EMLT) will be able to purify the patient’ blood from toxic substances and synthesize proteins needed for vital functions, improving survival and preventing severe complications, without the risk of rejection (thus eliminating the need for lifelong immunosuppression). If successful, such a pioneering approach will allow using a single stem cell population to manufacture an off-the-shelf, sustainable product to potentially treat thousands of people. We will conduct thorough pre-clinical studies assessing the efficacy and the short- and long-term safety of this product, in compliance with Health Canada requirements, in order to prepare for an early-phase clinical trial in the medium term (5 years). In collaboration our partners, the EMLT will be patented and options for its commercialization through a spin-off company creation or out-licensing to biopharmaceuticals companies will be explored. If successful, this project will deliver an innovative product to treat liver failure, with the potential of saving hundreds of thousands of patients worldwide. |
01/12/2016 |
31/12/2017 |
| 2016 |
Amy Zarzeczny (C) |
University of Regina |
Recherche d’impact, politique publique |
Caulfield |
Cochercheur |
Timothy Caulfield, Amy Zarzeczny |
5 000 |
Stem cells and misleading marketing claims |
QEJS, questions éthiques, juridiques et sociales |
|
The marketing of unproven stem cell therapies continues to be a major science and health policy issue. In addition to the hundreds of clinics throughout the world promoting scientifically questionable services, an increasing number of alternative providers are moving into the stem cell sphere (e.g., naturopaths, chiropractors). There is a range of social, scientific harms associated with this marketing trend, including, inter alia, physical harm to patients, financial exploitation, the creation of unrealistic expectations and public confusion about the state of the science. This Impact project will focus on options for curbing misleading marketing practices. To this end, we will: 1) provide an analysis of the claims and language associated with the marketing of unproven stem cell therapies (including the first ever analysis of alternative providers’ claims); 2) develop a comprehensive policy tool kit to address misleading claims (e.g., truth in advertising laws, consumer protection policies, professional norms, etc); and 3) work with professional regulators, consumer advocacy groups, and science policy makers to develop policy strategies, including the commencement of an enforcement test case. This project is a unique and much-needed initiative with the potential to have a real impact and provide actionable policy advice within a short timeframe. |
01/12/2016 |
31/12/2017 |
| 2016 |
Timothy Caulfield (P) |
University of Alberta |
Recherche d’impact, politique publique |
Caulfield |
Chercheur principal |
Timothy Caulfield, Amy Zarzeczny |
45 000 |
Stem cells and misleading marketing claims |
QEJS, questions éthiques, juridiques et sociales |
|
The marketing of unproven stem cell therapies continues to be a major science and health policy issue. In addition to the hundreds of clinics throughout the world promoting scientifically questionable services, an increasing number of alternative providers are moving into the stem cell sphere (e.g., naturopaths, chiropractors). There is a range of social, scientific harms associated with this marketing trend, including, inter alia, physical harm to patients, financial exploitation, the creation of unrealistic expectations and public confusion about the state of the science. This Impact project will focus on options for curbing misleading marketing practices. To this end, we will: 1) provide an analysis of the claims and language associated with the marketing of unproven stem cell therapies (including the first ever analysis of alternative providers’ claims); 2) develop a comprehensive policy tool kit to address misleading claims (e.g., truth in advertising laws, consumer protection policies, professional norms, etc); and 3) work with professional regulators, consumer advocacy groups, and science policy makers to develop policy strategies, including the commencement of an enforcement test case. This project is a unique and much-needed initiative with the potential to have a real impact and provide actionable policy advice within a short timeframe. |
01/12/2016 |
31/12/2017 |
| 2016 |
Judy Illes (P) |
University of British Columbia |
Recherche d’impact, politique publique |
Illes |
Chercheur principal |
Judy Illes |
50 000 |
Decision-making in translation: ugency, access, and evaluation in off-label stem cell interventions |
QEJS, questions éthiques, juridiques et sociales |
|
The development of health technologies traditionally follows a linear path from discovery through clinical research and, when successful, market approval. In the stem cell arena, however, the path is more multi-pronged than linear, and incorporates different points of access to interventions outside of clinical trials. This is a complex landscape that is especially important for stem cell procedures for as-yet unapproved medical reasons, also known as off-label use. In this study, we are specifically interested in the case of multiple sclerosis (MS) for which, following significant clinical trials activity, patients may be faced with decisions about off-label stem cell transplants. To narrow the gap in this understudied domain of off-label interventions, we will interview MS patients and explore with them the evaluative criteria and decision-making processes that lead them to an off-label bone marrow stem cell transplant over the more conventional alternatives of participating in a clinical trial or waiting for a market-approved therapy. We will deliver the knowledge we gain and its products in the form of evidence-informed resources and recommendations to patients and providers to elevate “informed” in the equation of “informed choices” about investigational stem cell products in the face of chronic, neurodegenerative disease. |
01/12/2016 |
31/12/2017 |
| 2016 |
Amy Zarzeczny (C) |
University of Regina |
Recherche d’impact, politique publique |
Ogbogu |
Cochercheur |
Ubaka Ogbogu, Amy Zarzeczny |
10 000 |
Regulating the future: model policies for emerging stem cell research activities, including research on gene-edited and reconstituted embryos |
QEJS, questions éthiques, juridiques et sociales |
|
Legislation governing research on human embryos in Canada, including stem cell derivation research, was enacted in 2004. Since then, a number of research techniques not directly addressed in the legislation have been described in the scientific literature. Two such techniques – the creation and use of genetically modified human embryos for research and the patterning of human induced pluripotent stem cells in a manner that may resemble post-implantation embryos – raise pressing questions both about the legality of these emerging techniques and about the appropriateness of current governance frameworks. More specifically, the growing interest in these emerging avenues of research highlight the need to reconsider Canada’s regulatory framework in the context of current scientific realities and to evaluate whether it adequately and appropriately addresses and balances the promotion of scientific and clinical progress with other key policy imperatives. Through a multi-disciplinary policy workshop supported by legal and policy analyses, this project will investigate two main questions: (1) whether, and, in what manner, should Canadian embryo and related research regulations be updated to reflect current research realities and scientific advances? and (2) what specific rules and governance mechanisms are required to ensure the ethical conduct of novel embryo-based research activities? The project will produce a consensus-based model policy and governance framework for regulating embryo research advances in Canada, academic publications and “policy briefing notes” designed for particular audiences, including legislators, scientists, media and the public. The project outcomes will have direct relevance to issues and research activities that affect or involve many Canadians, including scientists, governments and patients. |
01/12/2016 |
31/12/2017 |
| 2016 |
Ubaka Ogbogu (P) |
University of Alberta |
Recherche d’impact, politique publique |
Ogbogu |
Chercheur principal |
Ubaka Ogbogu, Amy Zarzeczny |
40 000 |
Regulating the future: model policies for emerging stem cell research activities, including research on gene-edited and reconstituted embryos |
QEJS, questions éthiques, juridiques et sociales |
|
Legislation governing research on human embryos in Canada, including stem cell derivation research, was enacted in 2004. Since then, a number of research techniques not directly addressed in the legislation have been described in the scientific literature. Two such techniques – the creation and use of genetically modified human embryos for research and the patterning of human induced pluripotent stem cells in a manner that may resemble post-implantation embryos – raise pressing questions both about the legality of these emerging techniques and about the appropriateness of current governance frameworks. More specifically, the growing interest in these emerging avenues of research highlight the need to reconsider Canada’s regulatory framework in the context of current scientific realities and to evaluate whether it adequately and appropriately addresses and balances the promotion of scientific and clinical progress with other key policy imperatives. Through a multi-disciplinary policy workshop supported by legal and policy analyses, this project will investigate two main questions: (1) whether, and, in what manner, should Canadian embryo and related research regulations be updated to reflect current research realities and scientific advances? and (2) what specific rules and governance mechanisms are required to ensure the ethical conduct of novel embryo-based research activities? The project will produce a consensus-based model policy and governance framework for regulating embryo research advances in Canada, academic publications and “policy briefing notes” designed for particular audiences, including legislators, scientists, media and the public. The project outcomes will have direct relevance to issues and research activities that affect or involve many Canadians, including scientists, governments and patients. |
01/12/2016 |
31/12/2017 |
| 2018 |
Jean Roy (P) |
Hôpital Maisonneuve-Rosemont |
Subventions de soutien des essais cliniques |
Roy |
Chercheur principal |
Jean Roy |
500 000 |
Allogeneic stem cell transplant using UM171 expanded cord bloods for patients with high-risk multiple myeloma |
Sang, myélome |
|
Multiple myeloma, the second most common blood cancer in Canada, remains incurable with a life expectancy of 5-6 years. Myeloma patients with advanced disease, chromosome abnormalities, myeloma cells in the blood or who are unresponsive to initial therapy have an even worse survival of approximately 3 years. To date, the only curative option for multiple myeloma is an allogeneic stem cell transplant (a transplant from a family or unrelated donor). However, allogeneic transplant is associated with serious side effects, the most significant being the donor cells attacking various recipient’s organs, a condition called graft-versus-host disease, leading to an early mortality of 10-20%. In patients who survive, long-term immune complications (80%) and relapse (50%) remain frequent. Clearly, allogeneic transplant needs to be improved in order to cure more patients.
In this study, we propose to use the unique properties of cord blood in order to make allogeneic transplant safer and more successful for myeloma patients. Cord blood use is associated with a much lower incidence of immune complications while having strong anti-cancer activity. It has been used for decades in children, less so in adults due to small number of stem cells in the graft leading to slow blood counts recovery after transplant. Recently, a novel molecule discovered by Canadian scientists in Montreal, UM171, has been shown to increase the number of stem cells and anti-cancer immune cells in laboratory, with promising results in the first 17 adults transplanted. In this study, cord bloods will be cultured in laboratory then infused in 10 patients with myeloma at higher risk of relapse. We expect a decreased incidence of immune complications and lower incidence of relapse. If successful, allogeneic transplant using cord bloods expanded with UM171 could become the treatment of choice for patients with poor prognosis multiple myeloma in the near future. |
01/04/2018 |
28/02/2019 |
| 2018 |
James Shapiro (P) |
University of Alberta |
Subventions de soutien des essais cliniques |
Shapiro |
Chercheur principal |
James Shapiro |
500 000 |
Pancreatic Progenitor Cell Therapy: Solving Supply and Survival Issues of Islet Cell Transplantation for T1DM |
Diabète |
|
The proposed project is aimed at treating, and functionally curing, type 1 diabetes mellitus (T1D) patients with embryonic stem cell-derived islet replacement therapy. There is no known way to prevent or cure T1D. Since the primary pathogenesis of T1D is the loss of the insulin-producing beta cells in the pancreas, it is a good candidate for cell replacement therapy. Cadaver islet transplantation represents clinical proof-of-concept for this approach, and the pluripotent stem cell-based technologies have the potential to solve the current shortage of material, as well as to provide reliable, high quality implantable material delivered in a safe and broadly applicable format.
The VC01 trial is designed to target all insulin-utilizing patients, including at least 270,000 Canadians and 40 million worldwide; the VC02 trial targets 10% T1D patients at high risk of acute complications. Both use the same pancreatic endoderm cells (PEC-01). These patients suffer insulin injection, hypoglycemia unawareness, and severe hypoglycemic episodes, which can be sometimes fatal. Medical care costs for people with diabetes are more than two times higher than for those without diabetes.
ViaCyte has made great progress in developing a practical islet cell replacement therapy, and the Edmonton Team has collaborated with them both in pre-clinical and clinical studies previously (VC01 cohort 1 and VC02 cohort 1 – SCN funded). The proposal herein is to perform clinical testing of an improved VC01 delivery device to demonstrate clinically relevant efficacy, and the VC02 in high-risk T1D patients (cohort 2) to assess safety and efficacy.
The project is likely the most expedient way to assess this therapy in T1D patients with the most urgent unmet medical need. VC01/VC02 products could transform and save the lives of countless people suffering with T1D, and eventually minimize the resource stress placed on our healthcare system. |
01/04/2018 |
28/02/2019 |
| 2018 |
Duncan Stewart (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien des essais cliniques |
Stewart |
Chercheur principal |
Duncan Stewart |
500 000 |
ENhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT- AMI) |
Cardiaque |
|
Rationale: Patients with a large area of damaged heart muscle after a heart attack have a high risk for heart failure and death. Cell-based gene therapy could restore working muscle in regions that otherwise would form only scar tissue, and lead to better heart repair and function.
Purpose: The primary objectives of the ENACT-AMI trial are to determine whether the administration of a patient’s own (autologous) Endothelial Progenitor Cells (EPCs) is safe and effective in improving cardiac function following large heart attack, and whether the use of cells that are genetically engineered by adding extra copies of a gene that is critical for blood vessel function and repair, namely endothelial Nitric Oxide Synthase (eNOS), is superior to non-modified cells. A secondary objective is to determine whether the benefit of EPC therapy depends on the timing of cell delivery (5-15 days versus 16-30 days post-STEMI).
Novel aspects: The use of the patient’s own cells avoids the immunological rejection that occurs with transplantation of cells from other individuals, but is greatly hampered by the fact that the reparative activities of stem and progenitor cells are negatively influenced by the host risk factors that lead to heart disease in the first place, namely advanced age, high cholesterol, diabetes and so forth. We have shown that adding extra copies of the eNOS gene (which protects blood vessels and promotes their growth and repair) can restore the activity of EPCs from heart patients by almost 90%. ENACT-AMI is the first clinical trial in the world to include a strategy designed to enhance the function of a patient’s own cells, and the first to use combination gene and cell therapy, for the treatment of heart disease.
Benefits to Canadians and Canada: While outcomes after heart attacks have greatly improved with the advent of modern therapies to open up the blocked coronary artery (reperfusion therapy), about 20% of patients fail to receive the expected benefits of reperfusion therapy, and face the consequences of large heart damage and subsequent heart failure. Should gene-enhanced EPCs provide an effective adjunctive treatment for these patients, this would avoid a high individual burden of chronic debilitating disease, while reducing the high costs to the health care system which in Canada totals $2.8 billion per year for heart failure (heartandstroke.ca/heartreport). If successful, ENACT investigators are well positioned to disseminate such a therapy across Canada though CellCAN, a unique network of cell manufacturing facilities across Canada. |
01/04/2018 |
28/02/2019 |
| 2018 |
Timothy Kieffer (P) |
University of British Columbia |
Recherche d’impact, clinical translation et accelerator |
Kieffer |
Chercheur principal |
Timothy Kieffer |
100 000 |
Assessment of Cell Maturation and Function in Subcutaneous Macroencapsulation Devices in Rodents |
Diabète |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Zachary Laksman (P) |
University of British Columbia |
Recherche d’impact, clinical translation et accelerator |
Laksman |
Chercheur principal |
Zachary Laksman, Glen Tibbits |
90 000 |
High throughput novel drug screening in human tissue model of atrial fibrillation |
Maladie du cœur, maladies du cœur, maladie cardiaque, maladies cardiaques |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Glen Tibbits (C) |
Simon Fraser University |
Recherche d’impact, clinical translation et accelerator |
Laksman |
Cochercheur |
Zachary Laksman, Glen Tibbits |
10 000 |
High throughput novel drug screening in human tissue model of atrial fibrillation |
Maladie du cœur, maladies du cœur, maladie cardiaque, maladies cardiaques |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Lauralyn McIntyre (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Recherche d’impact, clinical translation et accelerator |
McIntyre |
Chercheur principal |
Lauralyn McIntyre |
100 000 |
Cellular Immunotherapy for Septic Shock (CISS2): A Phase II Multicentre Clinical Trial |
Septicémie |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Bernard Thébaud (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Recherche d’impact, clinical translation et accelerator |
Thébaud |
Chercheur principal |
Bernard Thébaud |
99 905 |
Endothelial Progenitor Cell-derived Therapies for Neonatal Pulmonary Hypertension |
Maladie pulmonaire, maladies pulmonaires, maladie des poumons, maladies des poumons |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Glen Tibbits (P) |
Simon Fraser University |
Recherche d’impact, clinical translation et accelerator |
Tibbits |
Chercheur principal |
Glen Tibbits |
99 500 |
Developing an hiPSC-CM based protocol to investigate SIDS-implicated sudden cardiac arrest in infants |
Cardiaque |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Xudong Cao (C) |
Université d’Ottawa |
Recherche d’impact, clinical translation et accelerator |
Tsai |
Cochercheur |
Xudong Cao, Eve Tsai |
28 915 |
Translating an animal endogenous stem/progenitor cell repair strategy for stroke to humans |
Lésion cérébrale, traumatisme crânien, traumatisme cérébral |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Eve Tsai (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Recherche d’impact, clinical translation et accelerator |
Tsai |
Chercheur principal |
Xudong Cao, Eve Tsai |
71 085 |
Translating an animal endogenous stem/progenitor cell repair strategy for stroke to humans |
Lésion cérébrale, traumatisme crânien, traumatisme cérébral |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Derrick Rancourt (P) |
University of Calgary |
Recherche d’impact, commercialisation |
Rancourt |
Chercheur principal |
Derrick Rancourt |
100 000 |
Enhancing the Efficiency of Genome Engineering in Human Pluripotent Stem Cells |
Ingénierie génomique |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Peter Zandstra (P) |
University of British Columbia |
Recherche d’impact, commercialisation |
Zandstra |
Chercheur principal |
Peter Zandstra |
100 000 |
A robust, quantitative, and high-throughput assay to rapidly characterize human induced pluripotent stem cells. |
Caractérisation des CSPi |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Joanne Matsubara (P) |
University of British Columbia |
Équipes de recherche sur les maladies |
Matsubara |
Chercheur principal |
Joanne Matsubara |
100 000 |
Treating advanced retinal degeneration – rebuilding multiple co-dependent retinal layers in stem cells |
Oculaire |
|
Untreatable retinal degeneration dramatically affects millions of people, both young and old. In Canada, vision loss incurs the highest direct healthcare costs of any disease group – $33,000/patient/year. Globally, age-related macular degeneration (AMD) has an economic cost of over $350 billon (USD) annually, let alone the many other diseases that cause untreatable retinal degeneration.
Fortunately, stem-cell-based therapeutics are rapidly approaching the level of efficacy, safety, and economic scalability needed for clinical adoption. However, a central barrier remains for vision to be restored to the vast majority of patients that suffer from advanced retinal degeneration, that both the retinal pigment epithelium (RPE) and photoreceptor (PR) layers – co-dependant layers – must be regenerated. Unfortunately, these graft cells have not been shown to self-stratify and thus cannot be simply co-injected. Current best graft delivery efforts use scaffolds or sheets, which often do more harm than good or provide negligible coverage.
We have developed a cell-based therapeutic that addresses this translational roadblock by non-invasively inducing (via proprietary technology) dual-graft (RPE+PR) suspension injected into the subretinal space into polarized – stratified – layers with extensive fundus-coverage. This is achieved using standard clinical techniques and infrastructure, which reduces costs and increases likelihood of clinical adoption. We have attained dual-graft stratification in live rabbit trials. Despite these promising graft-architecture data, further optimization through larger-scale animal trials is required to obtain the efficacy and safety data to attract the considerable investment and partnerships needed to initiate clinical trials in Canada. Our core aims are: 1) generating dual-graft stratification in clinically relevant: graft (stem-cell-derived) and hosts (rabbits that have lost their PR layer), and 2) establishing graft integration (useful synapse formation) and vision benefit. In preparation for commercialization, our multidisciplinary team, representing three Canadian universities (UBC, SFU, and DU), have spun-off the company, VisuCyte Therapeutics Inc., which is being incubated at UBC. |
01/04/2018 |
28/02/2019 |
| 2018 |
Shirley Mei (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Équipes de recherche sur les maladies |
McIntyre |
Cochercheur |
Lauralyn McIntyre, Shirley Mei |
44 278 |
Cellular Immunotherapy for Septic Shock (CISS2): A phase II multicentre clinical trial |
Septicémie |
|
Septic shock is a common and devastating illness in the intensive care unit (ICU) accounting for approximately 20% of admissions, of which 30-40% will die. Survivors suffer long-term impairment in function and reduced quality of life (QOL). Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy. Mesenchymal stem cells (MSCs) represent a novel treatment and have been shown to calm the immune system, rid infection-causing organisms, restore organ function, and reduce death in septic animals.
Our team is the first in the World to have completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe in acutely ill patients and that a randomized controlled trial (RCT) is feasible. We are now moving to a Phase II RCT at several Canadian academic hospitals. This RCT will continue to evaluate safety and assess if there are strong signals for clinical benefit and determine mechanisms by which MSCs exert their positive effects. An economic analysis will also determine if the treatment is cost effective
Our multi-disciplinary team brings extensive experience in basic science, translational research, and early and late-phase clinical trialists. We are collaborating with the Canadian Critical Care Trials Group and Translational Biology Group, a prolific group of world-renowned investigators, and have established partnerships within the Ottawa Hospital Research Institute and Canadian Blood Services to develop a potent cryopreserved MSC product and to ensure its efficient distribution to participating centres. A strong signal for clinical benefit in the Phase II trial will be used to secure industrial partnership to support an international multi-centre Phase III cell therapy trial which if positive could result in saving thousands of lives and restoring the function and QOL of survivors of this devastating illness. |
01/04/2018 |
28/02/2019 |
| 2018 |
Lauralyn McIntyre (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Équipes de recherche sur les maladies |
McIntyre |
Chercheur principal |
Lauralyn McIntyre, Shirley Mei |
155 722 |
Cellular Immunotherapy for Septic Shock (CISS2): A phase II multicentre clinical trial |
Septicémie |
|
Septic shock is a common and devastating illness in the intensive care unit (ICU) accounting for approximately 20% of admissions, of which 30-40% will die. Survivors suffer long-term impairment in function and reduced quality of life (QOL). Despite decades of research examining different immune therapies, none has proven successful and supportive care remains the mainstay of therapy. Mesenchymal stem cells (MSCs) represent a novel treatment and have been shown to calm the immune system, rid infection-causing organisms, restore organ function, and reduce death in septic animals.
Our team is the first in the World to have completed a Phase I clinical trial that evaluated MSCs in patients with septic shock. Our trial established that MSCs appear safe in acutely ill patients and that a randomized controlled trial (RCT) is feasible. We are now moving to a Phase II RCT at several Canadian academic hospitals. This RCT will continue to evaluate safety and assess if there are strong signals for clinical benefit and determine mechanisms by which MSCs exert their positive effects. An economic analysis will also determine if the treatment is cost effective
Our multi-disciplinary team brings extensive experience in basic science, translational research, and early and late-phase clinical trialists. We are collaborating with the Canadian Critical Care Trials Group and Translational Biology Group, a prolific group of world-renowned investigators, and have established partnerships within the Ottawa Hospital Research Institute and Canadian Blood Services to develop a potent cryopreserved MSC product and to ensure its efficient distribution to participating centres. A strong signal for clinical benefit in the Phase II trial will be used to secure industrial partnership to support an international multi-centre Phase III cell therapy trial which if positive could result in saving thousands of lives and restoring the function and QOL of survivors of this devastating illness. |
01/04/2018 |
28/02/2019 |
| 2018 |
Cindi Morshead (C) |
University of Toronto |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 223 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Jing Wang (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Paul Frankland (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
David Kaplan (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Ann Yeh (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Doug Munoz (C) |
Queen's University |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Donald Mabbott (C) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Freda Miller (P) |
Hospital for Sick Children |
Équipes de recherche sur les maladies |
Miller |
Chercheur principal |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 222 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Wolfram Tetzlaff (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Miller |
Cochercheur |
Freda Miller, Donald Mabbott, Cindi Morshead, Doug Munoz, Ann Yeh, David Kaplan, Paul Frankland, Jing Wang, Wolfram Tetzlaff |
22 223 |
Pharmacological recruitment of endogenous neural precursors to promote pediatric white matter repair |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, we will translate this finding to the clinic. To do so, we will perform preclinical work with metformin in different mouse models of white matter damage, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. At the same time, we will pursue a pilot clinical trial of metformin for pediatric demyelinating disease using outcome measures we recently developed. To pursue these objectives, we have assembled an expert team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan and Doug Munoz) and clinician-scientists (Ann Yeh and Don Mabbott). Positive results in our clinical trial will lead to a dramatic shift in how we treat children/teenagers with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/04/2018 |
28/02/2019 |
| 2018 |
Massimiliano Paganelli (P) |
CHU Sainte-Justine |
Équipes de recherche sur les maladies |
Paganelli |
Chercheur principal |
Massimiliano Paganelli |
100 000 |
Safety and efficacy of stem cell- derived Encapsulated Liver Tissue to treat liver failure without immunosuppression |
Insuffisance hépatique |
|
One in ten Canadians is affected by liver disease. The standard of care for liver failure (the common outcome of any progressive liver disease) is liver transplantation, but only 400 transplants are performed each year in Canada for over 5000 liver deaths/year. Thus, there is an urgent need for new therapies capable of replacing liver functions in children and adults with liver failure. Thanks to a grant from the Stem Cell Network and to a team of internationally-renowned experts, in less than one year we developed an innovative stem cell-derived product capable of effectively performing the functions of the human liver. The final aim of this multidisciplinary project is to develop such a product into a treatment to restore the lacking liver functions in patients with liver failure, improving survival and preventing/treating complications. We will thoroughly assess the potential of our stem cell-derived product (what we call the encapsulated liver tissue, or ELT) to purify the patients’ blood from toxic substances and synthesize proteins needed for vital functions, improving survival and preventing severe complications, without the risk of rejection (eliminating the need for lifelong immunosuppression). If successful, at the end of the study we will dispose of a safe and effective off-the-shelf, implantable product to potentially treat thousands of people with liver failure. We will then conduct thorough pre-clinical studies, in compliance with Health Canada requirements, in order to prepare for an early-phase clinical trial in the medium term (3 years). We already protected this intellectual property and, in collaboration with our partners, we will work to translate the ELT to the industry through a start-up company creation or out-licensing. If successful, this project will deliver an innovative product to treat acute, chronic or acute-on-chronic liver failure without immunosuppression, with the potential of saving hundreds of thousands of patients worldwide. |
01/04/2018 |
28/02/2019 |
| 2018 |
Gregory Korbutt (C) |
University of Alberta |
Équipes de recherche sur les maladies |
Shapiro |
Cochercheur |
James Shapiro, Gregory Korbutt |
50 000 |
Development of a novel stem cell- derived transplant modality for type 1 diabetes |
Diabète |
|
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/04/2018 |
28/02/2019 |
| 2018 |
James Shapiro (P) |
University of Alberta |
Équipes de recherche sur les maladies |
Shapiro |
Chercheur principal |
James Shapiro, Gregory Korbutt |
50 000 |
Development of a novel stem cell- derived transplant modality for type 1 diabetes |
Diabète |
|
Islet transplantation has demonstrated that the replacement of insulin-producing β-cells is an effective means of restoring blood glucose control in patients with type 1 diabetes (T1D), especially in subjects at risk of severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors must be addressed. Remarkable progress has occurred in stem cell technology regarding clinical-grade insulin-producing cells with the capacity for limitless expansion; solving inadequate organ donor supply. Our group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s (world leader in stem cell development) VC-01 and VC-02 combination products in a cohort of patients with T1D in Edmonton. This trial examines the ability of ViaCyte’s insulin-producing pancreatic endoderm cells (PEC) to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into National and Worldwide clinical practice. The objective of this SCN proposal is to use an innovative approach to bioengineer a retrievable, functionalized scaffold, that houses and supports long-term function of ViaCyte’s PEC cells to treat T1D. The Disease Team consists of Dr. James Shapiro and Dr. Gregory Korbutt. As a clinical scientist and Director of the Clinical Islet Transplant Program, Dr. Shapiro is internationally recognized for his pioneering contributions to the development of the ‘Edmonton Protocol’, and is currently leading thirteen clinical trials in islet, stem cell and liver transplantation. Co-PI, Dr. Korbutt, is the Scientific Director of the cGMP “Alberta Cell Therapy Manufacturing Facility” for cell and tissue production, with significant expertise in islet biology and transplantation. The Team has also established a productive collaboration the Ingenuity Lab Nanotechnology Accelerator, with Dr. Puru Kuppan, a multidisciplinary R&D initiative focused on groundbreaking nanotechnology advances. Strategies for further commercialization will be conducted with support from TEC Edmonton, whom has provided support in filing US and Canadian provisional patents for this technology. This research proposal has been developed by a group of investigators offering unique expertise in clinical islet transplantation and stem cell biology, as well as biomaterial engineering expertise. With an active clinical islet transplant program in Edmonton, a new cGMP facility for the clinical grade production of cells, and the bioactive scaffold design expertise of the Ingenuity’s Laboratory, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/04/2018 |
28/02/2019 |
| 2018 |
Bruce Verchere (P) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Chercheur principal |
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings |
80 000 |
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/04/2018 |
28/02/2019 |
| 2018 |
Francis Lynn (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Cochercheur |
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings |
80 000 |
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/04/2018 |
28/02/2019 |
| 2018 |
Timothy Kieffer (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Cochercheur |
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings |
20 000 |
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/04/2018 |
28/02/2019 |
| 2018 |
Megan Levings (C) |
University of British Columbia |
Équipes de recherche sur les maladies |
Verchere |
Cochercheur |
Bruce Verchere, Timothy Kieffer, Ann Yeh, Megan Levings |
20 000 |
Genetic manipulation of hES- derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/04/2018 |
28/02/2019 |
| 2018 |
Jean-François Bouchard (C) |
Université de Montréal |
Équipes de recherche sur les maladies |
Bernier |
Cochercheur |
Gilbert Bernier, May Griffith, Jean-François Bouchard |
25 000 |
Human macula transplantation in a pre-clinical model of severe macular degeneration in macaques |
Oculaire |
|
Retinal degenerative diseases affect millions of people worldwide. However, few if any efficient treatments actually exist. In most cases, loss of visual function results from death of photoreceptors, the specialized cells involved in phototransduction. In macular degenerations, retinal dystrophies and late-stage retinitis pigmentosa, cone photoreceptors are lost. Cone photoreceptors are required for color, daylight and high-resolution central vision. The eye of primates contains a unique circular structure of ~5 mm of diameter called the macula and located near the centre of the retina. The macula is highly enriched in cone photoreceptors. Because human vision depends largely on the macula for most daylight activities, finding a therapy to restore macular function is important. Cell replacement therapy using stem cells as a source of new photoreceptors opens the possibility not only to stop disease progression but also to restore visual function. Using human pluripotent stem cells (hPSCs), we have developed a method to produce large numbers of human cone photoreceptors that self-organize to form a human macula-like tissue. We also have identified molecules that are predicted to improve graft integration in the host retina. Next, we have developed commercial contacts with a Canadian startup (StemAxon) to test and use a Universal donor induced hPSC (UiPSC) line that is in principle suitable for grafting in any person. A macula only exists in primates. For this, we will graft our human macula in the macular sub-retinal space of macaques having lost their central vision through cobalt chloride treatment. Graft integration and restoration of macaque's central vision will be monitored in living animals using OCT and multi-focal ERG apparatus as well as behavioral visual tests. If successful, these experiments will represent a proof-of-principle that macula transplantation can restore central vision in a non-human primate and constitute the framework for a Phase I clinical trial. |
01/04/2018 |
28/02/2019 |
| 2018 |
May Griffith (C) |
Université de Montréal |
Équipes de recherche sur les maladies |
Bernier |
Cochercheur |
Gilbert Bernier, May Griffith, Jean-François Bouchard |
25 000 |
Human macula transplantation in a pre-clinical model of severe macular degeneration in macaques |
Oculaire |
|
Retinal degenerative diseases affect millions of people worldwide. However, few if any efficient treatments actually exist. In most cases, loss of visual function results from death of photoreceptors, the specialized cells involved in phototransduction. In macular degenerations, retinal dystrophies and late-stage retinitis pigmentosa, cone photoreceptors are lost. Cone photoreceptors are required for color, daylight and high-resolution central vision. The eye of primates contains a unique circular structure of ~5 mm of diameter called the macula and located near the centre of the retina. The macula is highly enriched in cone photoreceptors. Because human vision depends largely on the macula for most daylight activities, finding a therapy to restore macular function is important. Cell replacement therapy using stem cells as a source of new photoreceptors opens the possibility not only to stop disease progression but also to restore visual function. Using human pluripotent stem cells (hPSCs), we have developed a method to produce large numbers of human cone photoreceptors that self-organize to form a human macula-like tissue. We also have identified molecules that are predicted to improve graft integration in the host retina. Next, we have developed commercial contacts with a Canadian startup (StemAxon) to test and use a Universal donor induced hPSC (UiPSC) line that is in principle suitable for grafting in any person. A macula only exists in primates. For this, we will graft our human macula in the macular sub-retinal space of macaques having lost their central vision through cobalt chloride treatment. Graft integration and restoration of macaque's central vision will be monitored in living animals using OCT and multi-focal ERG apparatus as well as behavioral visual tests. If successful, these experiments will represent a proof-of-principle that macula transplantation can restore central vision in a non-human primate and constitute the framework for a Phase I clinical trial. |
01/04/2018 |
28/02/2019 |
| 2018 |
Gilbert Bernier (P) |
Hôpital Maisonneuve-Rosemont |
Équipes de recherche sur les maladies |
Bernier |
Chercheur principal |
Gilbert Bernier, May Griffith, Jean-François Bouchard |
150 000 |
Human macula transplantation in a pre-clinical model of severe macular degeneration in macaques |
Oculaire |
|
Retinal degenerative diseases affect millions of people worldwide. However, few if any efficient treatments actually exist. In most cases, loss of visual function results from death of photoreceptors, the specialized cells involved in phototransduction. In macular degenerations, retinal dystrophies and late-stage retinitis pigmentosa, cone photoreceptors are lost. Cone photoreceptors are required for color, daylight and high-resolution central vision. The eye of primates contains a unique circular structure of ~5 mm of diameter called the macula and located near the centre of the retina. The macula is highly enriched in cone photoreceptors. Because human vision depends largely on the macula for most daylight activities, finding a therapy to restore macular function is important. Cell replacement therapy using stem cells as a source of new photoreceptors opens the possibility not only to stop disease progression but also to restore visual function. Using human pluripotent stem cells (hPSCs), we have developed a method to produce large numbers of human cone photoreceptors that self-organize to form a human macula-like tissue. We also have identified molecules that are predicted to improve graft integration in the host retina. Next, we have developed commercial contacts with a Canadian startup (StemAxon) to test and use a Universal donor induced hPSC (UiPSC) line that is in principle suitable for grafting in any person. A macula only exists in primates. For this, we will graft our human macula in the macular sub-retinal space of macaques having lost their central vision through cobalt chloride treatment. Graft integration and restoration of macaque's central vision will be monitored in living animals using OCT and multi-focal ERG apparatus as well as behavioral visual tests. If successful, these experiments will represent a proof-of-principle that macula transplantation can restore central vision in a non-human primate and constitute the framework for a Phase I clinical trial. |
01/04/2018 |
28/02/2019 |
| 2018 |
Timothy Caulfield (P) |
University of Alberta |
Recherche d’impact, politique publique |
Caulfield |
Chercheur principal |
Timothy Caulfield |
40 000 |
The Next Step: Specific Strategies for Addressing the Marketing of Unproven Stem Cell Therapies |
Thérapies non éprouvées |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Bartha Knoppers (P) |
Université McGill |
Recherche d’impact, politique publique |
Knoppers |
Chercheur principal |
Bartha Knoppers |
39 736 |
Reforming Canadian Stem Cell Policy: Moving Beyond the Assisted Human Reproduction Act (AHRA) |
QEJS, questions éthiques, juridiques et sociales |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Eric Marsault (C) |
University of Sherbrooke |
Recherche d’impact, translation |
Bentzinger |
Cochercheur |
Florian Bentzinger, Mannix Auger-Messier, Eric Marsault |
9 000 |
Apelinergic Compounds for the treatment of muscular dystrophy |
Dystrophie musculaire |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Mannix Auger-Messier (C) |
University of Sherbrooke |
Recherche d’impact, translation |
Bentzinger |
Cochercheur |
Florian Bentzinger, Mannix Auger-Messier, Eric Marsault |
7 000 |
Apelinergic Compounds for the treatment of muscular dystrophy |
Dystrophie musculaire |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Florian Bentzinger (P) |
University of Sherbrooke |
Recherche d’impact, translation |
Bentzinger |
Chercheur principal |
Florian Bentzinger, Mannix Auger-Messier, Eric Marsault |
83 000 |
Apelinergic Compounds for the treatment of muscular dystrophy |
Dystrophie musculaire |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Mick Bhatia (P) |
McMaster University |
Recherche d’impact, translation |
Bhatia |
Chercheur principal |
Mick Bhatia |
100 000 |
Identification of kinases and their target substrates in early human PSC specification |
Kinases |
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
Nicolas Dumont (P) |
CHU Sainte-Justine |
Recherche d’impact, translation |
Dumont |
Chercheur principal |
Nicolas Dumont |
100 000 |
Targeting muscle stem cells to mitigate Duchenne muscular dystrophy |
|
|
|
01/04/2018 |
28/02/2019 |
| 2018 |
John Hassell (P) |
McMaster University |
Recherche d’impact, translation |
Hassell |
Chercheur principal |
John Hassell |
99 500 |
HTR5A as a target for anticancer stem cell drug discovery |
Cancer du sein |
|
|
01/04/2018 |
28/02/2019 |
| 2020 |
Timothy Kieffer (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
40 000 |
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/01/2020 |
31/01/2022 |
| 2020 |
Megan Levings (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
40 000 |
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/01/2020 |
31/01/2022 |
| 2020 |
Francis Lynn (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
228 000 |
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/01/2020 |
31/01/2022 |
| 2020 |
Bruce Verchere (P) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Chercheur principal |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
292 000 |
Genetic manipulation of hES-derived insulin-producing cells to improve graft outcomes |
Diabète |
|
A cure for type 1 diabetes may lie in the replacement of insulin-producing cells by transplantation. Hundreds of patients worldwide (including 80 in Vancouver) have received transplants of islets–clusters of insulin-producing cells in the pancreas–enabling better blood glucose control without the need for insulin administration. Yet because there are not enough organ donors, new sources of insulin-producing cells are needed for the millions living with this disease. Moreover, most islet transplants fail within a few years, requiring patients to return to insulin injections. Two recent advances may transform cell therapy in diabetes. First, human insulin-producing cells can now be generated from stem cells in a laboratory dish within a few weeks. Second, the genes of cells can be engineered to produce proteins that may enhance their survival and function.
In the first year of SCN support, our team genetically engineered human embryonic stem cells so that they (i) no longer produced a protein that is toxic in diabetes and cell transplants; and (ii) produce a protein which turns off the immune attack on transplanted cells. In the second year of SCN support, we propose to differentiate these genetically engineered stem cells into human insulin-producing cells and to test them following transplantation into mouse models of diabetes.
Our goal is to produce a new and improved cell source for cell replacement therapy in diabetes, that can be tested in clinical trial in a few years. Such an advance could not only transform the lives of thousands of Canadians living with diabetes but also greatly reduce the tremendous economic and health burden that diabetes places on Canada today. |
01/01/2020 |
31/01/2022 |
| 2020 |
Nilesh Ghugre (C) |
University of Toronto |
Subventions de soutien à l’accélération de la transposition clinique |
Laflamme |
Cochercheur |
Michael Laflamme, Graham Wright, Nilesh Ghugre |
74 592 |
Heart Regeneration with Mature Ventricular Cardiomyocytes from Human Pluripotent Stem Cells |
Cardiaque |
|
Each year 70,000 Canadians suffer a heart attack (also known as a myocardial infarction or MI) accounting for the majority of the 50,000 new cases of heart failure diagnosed annually. After an MI, the damaged heart muscle is replaced by non-contractile scar tissue, and current treatment options for treating post-MI heart failure are aimed at reducing symptoms and disease progress, not restoring lost myocardium. Hence, the ability to “remuscularize” the infarct zone via the transplantation of cardiomyocytes (heart muscle cells) derived from human pluripotent stem cells (hPSCs) represents a potentially revolutionary new therapy for patients suffering from this disease with very high morbidity and mortality. Toward this goal, this proposal brings together a diverse team of investigators with complementary expertise in stem cell and developmental biology (Gordon Keller), cell transplantation (Michael Laflamme & Ren-Ke Li), cardiac imaging in large-animal models of myocardial infarction (Graham Wright & Nilesh Ghugre) and the surgical care of patients with ischemic heart disease (Terrence Yau). In past work, we have translated our protocols for the cardiogenic differentiation of hPSCs from the lab bench to large-scale production, and we have partnered with BlueRock Therapeutics, a recently launched biotechnology company with Toronto-based cell manufacturing facilities to further upscale and commercialize these technologies. The present application builds on these advances and specifically focuses on testing a more recently developed mature hPSC-derived cardiomyocyte population that we predict will greatly improve the safety and efficacy of cell transplantation. We will test these mature hPSC-derived cardiomyocytes in a translationally-relevant porcine model of post-infarct heart failure and will employ comprehensive endpoints including histology (host and graft tissue structure), MRI (infarct size and contractile function), as well as ECG recording and mapping studies (electrical function). The successful completion of this work will help advance this novel cell product toward a first-in-human clinical trial in post-MI heart failure and further establish Canada’s leadership role in cardiac regenerative medicine. |
01/01/2020 |
31/01/2022 |
| 2020 |
Graham Wright (C) |
University of Toronto |
Subventions de soutien à l’accélération de la transposition clinique |
Laflamme |
Cochercheur |
Michael Laflamme, Graham Wright, Nilesh Ghugre |
22 704 |
Heart Regeneration with Mature Ventricular Cardiomyocytes from Human Pluripotent Stem Cells |
Cardiaque |
|
Each year 70,000 Canadians suffer a heart attack (also known as a myocardial infarction or MI) accounting for the majority of the 50,000 new cases of heart failure diagnosed annually. After an MI, the damaged heart muscle is replaced by non-contractile scar tissue, and current treatment options for treating post-MI heart failure are aimed at reducing symptoms and disease progress, not restoring lost myocardium. Hence, the ability to “remuscularize” the infarct zone via the transplantation of cardiomyocytes (heart muscle cells) derived from human pluripotent stem cells (hPSCs) represents a potentially revolutionary new therapy for patients suffering from this disease with very high morbidity and mortality. Toward this goal, this proposal brings together a diverse team of investigators with complementary expertise in stem cell and developmental biology (Gordon Keller), cell transplantation (Michael Laflamme & Ren-Ke Li), cardiac imaging in large-animal models of myocardial infarction (Graham Wright & Nilesh Ghugre) and the surgical care of patients with ischemic heart disease (Terrence Yau). In past work, we have translated our protocols for the cardiogenic differentiation of hPSCs from the lab bench to large-scale production, and we have partnered with BlueRock Therapeutics, a recently launched biotechnology company with Toronto-based cell manufacturing facilities to further upscale and commercialize these technologies. The present application builds on these advances and specifically focuses on testing a more recently developed mature hPSC-derived cardiomyocyte population that we predict will greatly improve the safety and efficacy of cell transplantation. We will test these mature hPSC-derived cardiomyocytes in a translationally-relevant porcine model of post-infarct heart failure and will employ comprehensive endpoints including histology (host and graft tissue structure), MRI (infarct size and contractile function), as well as ECG recording and mapping studies (electrical function). The successful completion of this work will help advance this novel cell product toward a first-in-human clinical trial in post-MI heart failure and further establish Canada’s leadership role in cardiac regenerative medicine. |
01/01/2020 |
31/01/2022 |
| 2020 |
Michael Laflamme (P) |
University Health Network |
Subventions de soutien à l’accélération de la transposition clinique |
Laflamme |
Chercheur principal |
Michael Laflamme, Graham Wright, Nilesh Ghugre |
502 389 |
Heart Regeneration with Mature Ventricular Cardiomyocytes from Human Pluripotent Stem Cells |
Cardiaque |
|
Each year 70,000 Canadians suffer a heart attack (also known as a myocardial infarction or MI) accounting for the majority of the 50,000 new cases of heart failure diagnosed annually. After an MI, the damaged heart muscle is replaced by non-contractile scar tissue, and current treatment options for treating post-MI heart failure are aimed at reducing symptoms and disease progress, not restoring lost myocardium. Hence, the ability to “remuscularize” the infarct zone via the transplantation of cardiomyocytes (heart muscle cells) derived from human pluripotent stem cells (hPSCs) represents a potentially revolutionary new therapy for patients suffering from this disease with very high morbidity and mortality. Toward this goal, this proposal brings together a diverse team of investigators with complementary expertise in stem cell and developmental biology (Gordon Keller), cell transplantation (Michael Laflamme & Ren-Ke Li), cardiac imaging in large-animal models of myocardial infarction (Graham Wright & Nilesh Ghugre) and the surgical care of patients with ischemic heart disease (Terrence Yau). In past work, we have translated our protocols for the cardiogenic differentiation of hPSCs from the lab bench to large-scale production, and we have partnered with BlueRock Therapeutics, a recently launched biotechnology company with Toronto-based cell manufacturing facilities to further upscale and commercialize these technologies. The present application builds on these advances and specifically focuses on testing a more recently developed mature hPSC-derived cardiomyocyte population that we predict will greatly improve the safety and efficacy of cell transplantation. We will test these mature hPSC-derived cardiomyocytes in a translationally-relevant porcine model of post-infarct heart failure and will employ comprehensive endpoints including histology (host and graft tissue structure), MRI (infarct size and contractile function), as well as ECG recording and mapping studies (electrical function). The successful completion of this work will help advance this novel cell product toward a first-in-human clinical trial in post-MI heart failure and further establish Canada’s leadership role in cardiac regenerative medicine. |
01/01/2020 |
31/01/2022 |
| 2020 |
Zachary Laksman (P) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Laksman |
Chercheur principal |
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham |
292 000 |
Pipeline towards stem cell driven personalized medicine for atrial fibrillation |
Cardiaque; fibrillation auriculaire |
|
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation. |
01/01/2020 |
31/01/2022 |
| 2020 |
Gordon Keller (C) |
University Health Network |
Subventions de soutien à l’accélération de la transposition clinique |
Laksman |
Cochercheur |
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham |
30 000 |
Pipeline towards stem cell driven personalized medicine for atrial fibrillation |
Cardiaque |
|
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation. |
01/01/2020 |
31/01/2022 |
| 2020 |
Glen Tibbits (C) |
Simon Fraser University |
Subventions de soutien à l’accélération de la transposition clinique |
Laksman |
Cochercheur |
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham |
152 000 |
Pipeline towards stem cell driven personalized medicine for atrial fibrillation |
Cardiaque |
|
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation. |
01/01/2020 |
31/01/2022 |
| 2020 |
Liam Brunham (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Laksman |
Cochercheur |
Zachary Laksman, Gordon Keller, Glen Tibbits, Liam Brunham |
112 000 |
Pipeline towards stem cell driven personalized medicine for atrial fibrillation |
Cardiaque |
|
Our international team of collaborators and industry partners are dedicated to delivering personalized therapy to patients with atrial fibrillation (AF). This first proof of principle study will take one family through the process of generating patient specific heart models, using both stem cell derived heart tissue and complex computational modeling, to identify therapies that have the most potential for benefit, while ultimately exposing individuals to the smallest risk of harm. Every step of this process requires unique expertise, technologic innovation, and provides for the opportunity for clinically impactful discovery. This can only be accomplished when clinicians, scientists, and industry partner together along a common vision, and focused on specific and tangible deliverables.
AF is the most common heart rhythm disorder, and has devastating consequences on patients and our health care system. While medications remain as first line therapy for AF, there has been an appalling paucity of new compounds over the last two decades. Current therapies remain ineffective, untargeted, and in many cases, unsafe. Companies have struggled to innovate and translate in this space because they have not had appropriate disease models before proceeding to expensive clinical trials. AF is a complex condition that requires the study of human heart tissue. We also know that changes in DNA have an important effect on the disease and its treatment.
Stem cell derived heart tissue has clearly superseded previous models of heart rhythm disorders, and is the only tool capable of studying a disease on a patient specific level. We generated the world’s first stem cell derived model of atrial fibrillation and have used this model system to replicate the clinical effects of commonly used heart medications, as well as show the potential toxic effects of a number of different compounds. Our team has grown to facilitate the requisite scaling of our model in order to provide a path towards clinically impactful deliverables. This includes expertise in bioengineered heart tissue, robotic automated high throughput screening, and whole organ computational modeling of disease. We are now uniquely positioned to provide clinically relevant solutions to patients suffering with atrial fibrillation. |
01/01/2020 |
31/01/2022 |
| 2020 |
Greg Korbutt (C) |
University of Alberta |
Subventions de soutien à l’accélération de la transposition clinique |
Nostro |
Cochercheur |
Cristina Nostro, Andrew Pepper, Greg Korbutt |
150 000 |
Co-localized hiPSC-derived beta cells and immunosuppression-loaded micelles as a novel approach for T1D treatment |
Diabète |
|
Islet transplantation has demonstrated that the replacement of β-cells is an effective means to treat T1D patients with severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors and issues associated with harsh immunosuppression must be addressed. As a result of the remarkable progress in stem cell technology, the Edmonton Group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s VC-01 and VC-02 combination products in a cohort of patients with T1D. This trial examines the ability of ViaCyte’s pancreatic endoderm cells to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into clinical practice. Furthermore, the development of alternative GMP grade hiPSC-derived β-cells is imperative for the future of β-cell transplantation. The objective of this proposal is to use an innovative approach to bioengineer localized drug delivery platforms and to support long-term function of β-cells to treat T1D. This research proposal has been developed by a group of investigators (Nostro, Korbutt and Pepper) who each offer unique expertise in clinical islet transplantation, stem cell biology and biomaterial engineering. Dr. Nostro is internationally recognized for her pioneering contributions to the development of β-cell derived from hESC and hiPSC. Dr. Korbutt is the Scientific Director of the “Alberta Cell Therapy Manufacturing Facility” with significant expertise in islet biology and transplantation. Dr. Pepper is an expert in islet and stem cell transplantation with a clear and well-proven path to translate pre-clinical discovery into curative treatments for T1D patients. Strategies for further commercialization will be conducted with support from TEC Edmonton and UHN, who have provided support in filing US and Canadian provisional patents for this technology. With the advances and IPs in stem cell differentiaton to β-cells, an active clinical islet transplant program in Edmonton, a new cGMP facility for clinical grade production of cells, and the in-house drug delivery fabrication expertise, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/01/2020 |
31/01/2022 |
| 2020 |
Andrew Pepper (C) |
University of Alberta |
Subventions de soutien à l’accélération de la transposition clinique |
Nostro |
Cochercheur |
Cristina Nostro, Andrew Pepper, Greg Korbutt |
150 000 |
Co-localized hiPSC-derived beta cells and immunosuppression-loaded micelles as a novel approach for T1D treatment |
Diabète |
|
Islet transplantation has demonstrated that the replacement of β-cells is an effective means to treat T1D patients with severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors and issues associated with harsh immunosuppression must be addressed. As a result of the remarkable progress in stem cell technology, the Edmonton Group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s VC-01 and VC-02 combination products in a cohort of patients with T1D. This trial examines the ability of ViaCyte’s pancreatic endoderm cells to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into clinical practice. Furthermore, the development of alternative GMP grade hiPSC-derived β-cells is imperative for the future of β-cell transplantation. The objective of this proposal is to use an innovative approach to bioengineer localized drug delivery platforms and to support long-term function of β-cells to treat T1D. This research proposal has been developed by a group of investigators (Nostro, Korbutt and Pepper) who each offer unique expertise in clinical islet transplantation, stem cell biology and biomaterial engineering. Dr. Nostro is internationally recognized for her pioneering contributions to the development of β-cell derived from hESC and hiPSC. Dr. Korbutt is the Scientific Director of the “Alberta Cell Therapy Manufacturing Facility” with significant expertise in islet biology and transplantation. Dr. Pepper is an expert in islet and stem cell transplantation with a clear and well-proven path to translate pre-clinical discovery into curative treatments for T1D patients. Strategies for further commercialization will be conducted with support from TEC Edmonton and UHN, who have provided support in filing US and Canadian provisional patents for this technology. With the advances and IPs in stem cell differentiaton to β-cells, an active clinical islet transplant program in Edmonton, a new cGMP facility for clinical grade production of cells, and the in-house drug delivery fabrication expertise, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/01/2020 |
31/01/2022 |
| 2020 |
Cristina Nostro (P) |
University Health Network |
Subventions de soutien à l’accélération de la transposition clinique |
Nostro |
Chercheur principal |
Cristina Nostro, Andrew Pepper, Greg Korbutt |
300 000 |
Co-localized hiPSC-derived beta cells and immunosuppression-loaded micelles as a novel approach for T1D treatment |
Diabète |
|
Islet transplantation has demonstrated that the replacement of β-cells is an effective means to treat T1D patients with severe complications. If this therapeutic approach is to be expanded to a wider spectrum of patients, then the scarcity of organ donors and issues associated with harsh immunosuppression must be addressed. As a result of the remarkable progress in stem cell technology, the Edmonton Group is currently conducting a first-in-human pilot phase 1/2 clinical trials to test ViaCyte’s VC-01 and VC-02 combination products in a cohort of patients with T1D. This trial examines the ability of ViaCyte’s pancreatic endoderm cells to survive and function in an immune protecting device transplanted under the skin. However, there is an essential need to further optimize this approach prior to its translation into clinical practice. Furthermore, the development of alternative GMP grade hiPSC-derived β-cells is imperative for the future of β-cell transplantation. The objective of this proposal is to use an innovative approach to bioengineer localized drug delivery platforms and to support long-term function of β-cells to treat T1D. This research proposal has been developed by a group of investigators (Nostro, Korbutt and Pepper) who each offer unique expertise in clinical islet transplantation, stem cell biology and biomaterial engineering. Dr. Nostro is internationally recognized for her pioneering contributions to the development of β-cell derived from hESC and hiPSC. Dr. Korbutt is the Scientific Director of the “Alberta Cell Therapy Manufacturing Facility” with significant expertise in islet biology and transplantation. Dr. Pepper is an expert in islet and stem cell transplantation with a clear and well-proven path to translate pre-clinical discovery into curative treatments for T1D patients. Strategies for further commercialization will be conducted with support from TEC Edmonton and UHN, who have provided support in filing US and Canadian provisional patents for this technology. With the advances and IPs in stem cell differentiaton to β-cells, an active clinical islet transplant program in Edmonton, a new cGMP facility for clinical grade production of cells, and the in-house drug delivery fabrication expertise, this team is well positioned to rapidly transfer our novel findings to clinical trials. |
01/01/2020 |
31/01/2022 |
| 2020 |
Vincent-Philippe Lavallee (C) |
Université de Montréal |
Subventions de soutien à l’accélération de la transposition clinique |
Sauvageau |
Cochercheur |
Guy Sauvageau, Vincent-Philippe Lavallee |
28 200 |
UM171 expansion improves the curative attributes of bone marrow stem cell grafts |
Sang |
|
Hematopoietic stem cells (HSC) transplantation is one of the most effective therapeutic strategies for patients with hematological malignancies. Largely supported by the SCN, our group of collaborators developed a cord blood (CB)-derived HSC expansion solution that includes the UM171 molecule and a Fed-batch HSC expansion system both of which combined have had major impact on CB transplantation. Indeed, to date more than 50 patients have received UM171/Fed-batch-expanded CB grafts with very promising results including low incidence of transplant-related mortality, chronic graft versus host disease and relapse rate. One of the key attributes of UM171/Fed-batch expanded CB is the inclusion of large numbers of immuno-modulatory cells, which we believe contribute to the success of these transplants. With the view of extending these attributes to bone marrow (BM) transplants, which are much more numerous than CB and hence further increasing the clinical impact of this procedure, we now propose three well-defined experimental aims:
First, we will develop a large-scale manufacturing process that will enable the production of UM171 expanded bone marrow grafts for our future clinical trial.
Second, considering our recent work showing that UM171 treatment of BM HSCs results in a marked increase in their ability to repopulate the thymus of humanized mice, we now intend to carefully characterize this important effect and verify if it is preserved in BM grafts derived from older donors which are typically associated with poor lymphoid function and clinical outcome. This will enable us to determine the optimal donor age in which this unique effect of UM171 is found and refine the design of our future clinical trial.
Third, we plan to characterize the cellular subpopulations in UM171-expanded BM grafts using state of the art technology, including CITE-Seq and preclinical functional assays. These essential preclinical studies will provide some understanding of the clinical impact of UM171 transplants and address regulatory issues associated with graft expansion.
These three aims represent an essential prerequisite of an optimal future clinical trial of UM171 bone marrow stem cell expansion whose final design will also be drafted using support and results from this grant. |
01/09/2020 |
28/02/2022 |
| 2020 |
Guy Sauvageau (P) |
Université de Montréal |
Subventions de soutien à l’accélération de la transposition clinique |
Sauvageau |
Chercheur principal |
Guy Sauvageau, Vincent-Philippe Lavallee |
371 800 |
UM171 expansion improves the curative attributes of bone marrow stem cell grafts |
Sang; leucémie |
|
Hematopoietic stem cells (HSC) transplantation is one of the most effective therapeutic strategies for patients with hematological malignancies. Largely supported by the SCN, our group of collaborators developed a cord blood (CB)-derived HSC expansion solution that includes the UM171 molecule and a Fed-batch HSC expansion system both of which combined have had major impact on CB transplantation. Indeed, to date more than 50 patients have received UM171/Fed-batch-expanded CB grafts with very promising results including low incidence of transplant-related mortality, chronic graft versus host disease and relapse rate. One of the key attributes of UM171/Fed-batch expanded CB is the inclusion of large numbers of immuno-modulatory cells, which we believe contribute to the success of these transplants. With the view of extending these attributes to bone marrow (BM) transplants, which are much more numerous than CB and hence further increasing the clinical impact of this procedure, we now propose three well-defined experimental aims:
First, we will develop a large-scale manufacturing process that will enable the production of UM171 expanded bone marrow grafts for our future clinical trial.
Second, considering our recent work showing that UM171 treatment of BM HSCs results in a marked increase in their ability to repopulate the thymus of humanized mice, we now intend to carefully characterize this important effect and verify if it is preserved in BM grafts derived from older donors which are typically associated with poor lymphoid function and clinical outcome. This will enable us to determine the optimal donor age in which this unique effect of UM171 is found and refine the design of our future clinical trial.
Third, we plan to characterize the cellular subpopulations in UM171-expanded BM grafts using state of the art technology, including CITE-Seq and preclinical functional assays. These essential preclinical studies will provide some understanding of the clinical impact of UM171 transplants and address regulatory issues associated with graft expansion.
These three aims represent an essential prerequisite of an optimal future clinical trial of UM171 bone marrow stem cell expansion whose final design will also be drafted using support and results from this grant. |
01/09/2020 |
28/02/2022 |
| 2020 |
Greg Korbutt (C) |
University of Alberta |
Subventions de soutien à l’accélération de la transposition clinique |
Shapiro |
Cochercheur |
James Shapiro, Greg Korbutt |
49 750 |
Autologous Patient-derived Islets from Induced Pluripotent Stem Cells (iPSC): The Next Generation Diabetes Therapy |
Diabète |
|
The University of Alberta under Dr. Shapiro’s direction has established a global presence as a leader in islet transplantation for T1D. Islet transplantation has a proven track record of success in effectively eradicating the risk of hypoglycemia while rendering many patients insulin free for variable periods. The downside, however, is the need for life-long immunosuppression, and a limited ability to isolate a full normal complement of islet mass to engraft in the recipient, as well as an insufficient organ donor pool requirement to meet the demand if indications for islet transplantation move beyond the select few with ‘brittle’ control. In contrast, human induced pluripotent stem cells (iPSCs) offer considerable promise as a renewable autologous β-cell source for transplantation without the need for chronic life-long immunosuppression. Human iPSC-derived β-cells have previously been shown to effectively control blood sugar and reverse diabetes in mice. In this proposal, we aim to validate human-derived autologous expanded iPSCs for generating β-like cells sourced from normal controls, patients with T1D, T2D and those with surgical diabetes after TP using established protocols, without the need for maintenance immune suppression. The purpose of using subjects with surgical diabetes, as controls, is to avoid potential initial challenges with either autoimmunity (in T1D) or insulin resistance (in T2D). The aim of the project is to evaluate iPSC-derived immature progenitor cells versus more mature functional β-like cells for scale-up. The ultimate goal is to establish GMP manufacturing processes to initiate a clinical trial for subcutaneous (phase 1 safety) followed by intraportal (phase 1/2 safety + efficacy) transplantation of autologous self-expanded β-like cells into TP patients, without immunosuppression, succeeded by transplantation in T2D and T1D patients.
The proposal shows strong potential for developing autologous cell therapy for the curative treatment of diabetes. Efforts to scale up GMP-grade iPSC-derived β-like cells will impart social benefit to Canadians and significantly relieve the current ever-increasing economic burden of diabetes healthcare in Canada. Our project team includes excellent researchers, clinicians and highly skilled technicians with stem cell expertise. In addition, we will collaborate with experts in islet regeneration, molecular genetics, transplant immunology, and GMP cell manufacturing. |
01/09/2020 |
28/02/2022 |
| 2020 |
James Shapiro (P) |
University of Alberta |
Subventions de soutien à l’accélération de la transposition clinique |
Shapiro |
Chercheur principal |
James Shapiro, Greg Korbutt |
350 250 |
Autologous Patient-derived Islets from Induced Pluripotent Stem Cells (iPSC): The Next Generation Diabetes Therapy |
Diabète |
|
The University of Alberta under Dr. Shapiro’s direction has established a global presence as a leader in islet transplantation for T1D. Islet transplantation has a proven track record of success in effectively eradicating the risk of hypoglycemia while rendering many patients insulin free for variable periods. The downside, however, is the need for life-long immunosuppression, and a limited ability to isolate a full normal complement of islet mass to engraft in the recipient, as well as an insufficient organ donor pool requirement to meet the demand if indications for islet transplantation move beyond the select few with ‘brittle’ control. In contrast, human induced pluripotent stem cells (iPSCs) offer considerable promise as a renewable autologous β-cell source for transplantation without the need for chronic life-long immunosuppression. Human iPSC-derived β-cells have previously been shown to effectively control blood sugar and reverse diabetes in mice. In this proposal, we aim to validate human-derived autologous expanded iPSCs for generating β-like cells sourced from normal controls, patients with T1D, T2D and those with surgical diabetes after TP using established protocols, without the need for maintenance immune suppression. The purpose of using subjects with surgical diabetes, as controls, is to avoid potential initial challenges with either autoimmunity (in T1D) or insulin resistance (in T2D). The aim of the project is to evaluate iPSC-derived immature progenitor cells versus more mature functional β-like cells for scale-up. The ultimate goal is to establish GMP manufacturing processes to initiate a clinical trial for subcutaneous (phase 1 safety) followed by intraportal (phase 1/2 safety + efficacy) transplantation of autologous self-expanded β-like cells into TP patients, without immunosuppression, succeeded by transplantation in T2D and T1D patients.
The proposal shows strong potential for developing autologous cell therapy for the curative treatment of diabetes. Efforts to scale up GMP-grade iPSC-derived β-like cells will impart social benefit to Canadians and significantly relieve the current ever-increasing economic burden of diabetes healthcare in Canada. Our project team includes excellent researchers, clinicians and highly skilled technicians with stem cell expertise. In addition, we will collaborate with experts in islet regeneration, molecular genetics, transplant immunology, and GMP cell manufacturing. |
01/09/2020 |
28/02/2022 |
| 2020 |
Glen Tibbits (P) |
Simon Fraser University |
Subventions de soutien à l’accélération de la transposition clinique |
Tibbits |
Chercheur principal |
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem |
217 415 |
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) |
Cardiaque |
Rare disease status |
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT. |
01/09/2020 |
28/02/2022 |
| 2020 |
Francis Lynn (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Tibbits |
Cochercheur |
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem |
33 210 |
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) |
Cardiaque |
Rare disease status |
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT. |
01/09/2020 |
28/02/2022 |
| 2020 |
Shubhayan Sanatani (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Tibbits |
Cochercheur |
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem |
51 450 |
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) |
Cardiaque |
Rare disease status |
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT. |
01/09/2020 |
28/02/2022 |
| 2020 |
Filip van Petegem (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Tibbits |
Cochercheur |
Glen Tibbits, Francis Lynn, Shubhayan Sanatani, Filip van Petegem |
97 875 |
Developing a hiPSC-CM based model for personalized treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT) |
Cardiaque |
Rare disease status |
CPVT is a severe heart disorder that affects 1 in 10,000 people. It causes abnormal rapid beating of the heart, which can cause sudden unexpected death, often without warning signs. CPVT is called “the perfect electrical assassin” because many will go into sudden cardiac arrest without being aware that they were at risk and nearly half of affected people will die before 35 years of age.
Our established team of scientists and cardiologists is recognized for our work on CPVT. In this project, we will use stem cell technology to convert patient blood samples into heart cells (hiPSC-CMs) that carry each patient’s genetic characteristics. We will use these engineered hiPSC-CMs to identify individual genetic causes of CPVT and to develop specific treatments for each patient. Ultimately, we want to create a way to test each patient’s risk so that we can prevent unexpected early death from CPVT. |
01/09/2020 |
28/02/2022 |
| 2020 |
Paul Frankland (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
53 333 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
David Kaplan (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
53 333 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Donald Mabbott (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
25 000 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Freda Miller (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
53 333 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Cindi Morshead (C) |
University of Toronto |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
53 333 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Douglas Munoz (C) |
Queen's University |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
25 000 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Jiwon Oh (C) |
University of Toronto |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
5 000 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Jing Wang (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
53 332 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Ann Yeh (P) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Chercheur principal |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
25 000 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales; sclérose en plaques |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Wolfram Tetzlaff (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Yeh |
Cochercheur |
Ann Yeh, Jing Wang, Jiwon Oh, Douglas Munoz, Cindi Morshead, Freda Miller, Donald Mabbott, David Kaplan, Paul Frankland, Wolfram Tetzlaff |
53 333 |
Pharmacological recruitment of endogenous neural precursors to promote white matter repair in MS |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
Damage to white matter in the brain occurs following injury and in disorders like multiple sclerosis, and results in sensory, motor, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation by enhancing the genesis of new oligodendrocytes, the cells that make myelin, and in so doing to promote white matter repair. To do this, we will take advantage of the fact that our brains contain resident precursor cells that normally make oligodendrocytes throughout life, and will ask whether we can pharmacologically activate these endogenous precursors to promote repair. Excitingly, our team has discovered that a widely-used and safe drug, metformin, will enhance the genesis of oligodendrocytes from neural precursors and that, following pediatric neural injury, this promotes neuroanatomical and functional recovery. In this proposal, first, we will perform preclinical work evaluating metformin’s effects on different mouse models of demyelination, and will search for additional methods of enhancing oligodendrocyte formation, since combinatorial approaches for treating white matter damage will likely be the most efficacious. In our final aim, we will pursue a pilot feasibility trial of metformin for children and young adults with demyelinating disease using outcome measures we have developed. To pursue this, we have assembled an expert Canadian team including basic scientists (Cindi Morshead, Jing Wang, Paul Frankland, Freda Miller, Wolfram Tetzlaff, David Kaplan, and Douglas Munoz) and clinician scientists (E. Ann Yeh, Donald Mabbott, Jiwon Oh and Giulia Longoni). Positive results in our clinical trial will lead to a dramatic shift in how we treat children and young adults with white matter injury, and will pave the way for future additional clinical trials in children and adults with white matter damage. |
01/09/2020 |
28/02/2022 |
| 2020 |
Jonas Mattsson (C) |
University Health Network |
Subventions de soutien à l’accélération de la transposition clinique |
Zúñiga-Pflücker |
Cochercheur |
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson |
80 000 |
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTImm) |
Sang |
|
Current standard cancer treatments for patients receiving hematopoietic stem cell transplant (HSCT) involve the use of chemotherapy and/or radiation. While most subsets of immune cells recover quickly, T-cells, which are key components of the immune system, remain absent or at low levels for many months to years, especially in the elderly. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects lengthy treatment with antibiotics and antivirals, and in some cases an infusion of donor T-cells are required. However, donor T-cells may also attack healthy tissues and cause graft-versus-host disease that in serious cases can lead to organ failure and death. Therefore, complications as a result of lack of T-cells or presence of donor T-cells can very adversely affect patients’ health.
To provide these patients with a much-needed T-cell boost, using our innovative DL4-μbead approach, we can now generate progenitor T-cells from donor blood stem cells in culture. This method will help speed replenishment of T-cells in post-transplant patients as infused progenitor T-cells will seed the thymus of patient, where they develop into mature T cells. Progenitor T-cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Preclinical studies in animal models have demonstrated that this is an effective and potentially curative treatment. Hence, progenitor T-cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
In short, our novel method possesses an enormous potential to not only improve the immune function but also to transform the field of hematopoietic transplantation in that: 1) proT cells will reduce mortality and disease leading to decreased instances of hospitalization; 2) it will reduce the current need for BM-derived HSC donations by directly increasing the number of proT cells precursors; and 3) it will permit the establishment of personalized immunotherapy through genetic manipulation of proT cells. These innovative outcomes will transform how immune- reconstitution is achieved in cancer patients. |
01/09/2020 |
28/02/2022 |
| 2020 |
Donna Wall (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Zúñiga-Pflücker |
Cochercheur |
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson |
80 000 |
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTImm) |
Sang |
|
Current standard cancer treatments for patients receiving hematopoietic stem cell transplant (HSCT) involve the use of chemotherapy and/or radiation. While most subsets of immune cells recover quickly, T-cells, which are key components of the immune system, remain absent or at low levels for many months to years, especially in the elderly. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects lengthy treatment with antibiotics and antivirals, and in some cases an infusion of donor T-cells are required. However, donor T-cells may also attack healthy tissues and cause graft-versus-host disease that in serious cases can lead to organ failure and death. Therefore, complications as a result of lack of T-cells or presence of donor T-cells can very adversely affect patients’ health.
To provide these patients with a much-needed T-cell boost, using our innovative DL4-μbead approach, we can now generate progenitor T-cells from donor blood stem cells in culture. This method will help speed replenishment of T-cells in post-transplant patients as infused progenitor T-cells will seed the thymus of patient, where they develop into mature T cells. Progenitor T-cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Preclinical studies in animal models have demonstrated that this is an effective and potentially curative treatment. Hence, progenitor T-cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
In short, our novel method possesses an enormous potential to not only improve the immune function but also to transform the field of hematopoietic transplantation in that: 1) proT cells will reduce mortality and disease leading to decreased instances of hospitalization; 2) it will reduce the current need for BM-derived HSC donations by directly increasing the number of proT cells precursors; and 3) it will permit the establishment of personalized immunotherapy through genetic manipulation of proT cells. These innovative outcomes will transform how immune- reconstitution is achieved in cancer patients. |
01/09/2020 |
28/02/2022 |
| 2020 |
Juan Carlos Zúñiga-Pflücker (P) |
Sunnybrook Research Institute |
Subventions de soutien à l’accélération de la transposition clinique |
Zúñiga-Pflücker |
Chercheur principal |
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson |
240 000 |
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTImm) |
Sang; immunothérapie pour le cancer, immunothérapies |
|
Current standard cancer treatments for patients receiving hematopoietic stem cell transplant (HSCT) involve the use of chemotherapy and/or radiation. While most subsets of immune cells recover quickly, T-cells, which are key components of the immune system, remain absent or at low levels for many months to years, especially in the elderly. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects lengthy treatment with antibiotics and antivirals, and in some cases an infusion of donor T-cells are required. However, donor T-cells may also attack healthy tissues and cause graft-versus-host disease that in serious cases can lead to organ failure and death. Therefore, complications as a result of lack of T-cells or presence of donor T-cells can very adversely affect patients’ health.
To provide these patients with a much-needed T-cell boost, using our innovative DL4-μbead approach, we can now generate progenitor T-cells from donor blood stem cells in culture. This method will help speed replenishment of T-cells in post-transplant patients as infused progenitor T-cells will seed the thymus of patient, where they develop into mature T cells. Progenitor T-cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Preclinical studies in animal models have demonstrated that this is an effective and potentially curative treatment. Hence, progenitor T-cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse.
In short, our novel method possesses an enormous potential to not only improve the immune function but also to transform the field of hematopoietic transplantation in that: 1) proT cells will reduce mortality and disease leading to decreased instances of hospitalization; 2) it will reduce the current need for BM-derived HSC donations by directly increasing the number of proT cells precursors; and 3) it will permit the establishment of personalized immunotherapy through genetic manipulation of proT cells. These innovative outcomes will transform how immune- reconstitution is achieved in cancer patients. |
01/09/2020 |
28/02/2022 |
| 2020 |
Manuel Caruso (C) |
Université Laval |
Subventions de soutien à l’accélération de la transposition clinique |
Germain |
Cochercheur |
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso |
12 000 |
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction |
Peau |
Rare disease status |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/09/2020 |
28/02/2022 |
| 2020 |
Bartha Knoppers (C) |
Université McGill |
Subventions de soutien à l’accélération de la transposition clinique |
Germain |
Cochercheur |
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso |
30 000 |
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction |
Peau |
Rare disease status |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/09/2020 |
28/02/2022 |
| 2020 |
Elena Pope (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Germain |
Cochercheur |
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso |
6 000 |
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction |
Peau |
Rare disease status |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/09/2020 |
28/02/2022 |
| 2020 |
Lucie Germain (P) |
Université Laval |
Subventions de soutien à l’accélération de la transposition clinique |
Germain |
Chercheur principal |
Lucie Germain, Elena Pope, Bartha Knoppers, Manuel Caruso |
352 000 |
Towards an epidermolysis bullosa clinical trial with tissue-engineered skin after ex vivo gene therapy correction |
Peau; épidermolyse bulleuse |
Rare disease status |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. At present, there is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life.
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a cure for RDEB. Our interdisciplinary team brings together: two fundamental investigators, including an expert in stem cells and tissue engineering and a specialist in gene therapy, an expert in socio-ethical and legal issues, a pediatric dermatologist, the medical director of the largest Canadian EB clinic and many research professionals experienced in the clinical translation of tissue engineering products. Thus, our infrastructure, expertise and knowledge will ensure the success of this project.
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. In order to develop a treatment for RDEB, our strategy is to produce self-assembled skin substitutes from autologous RDEB cells previously corrected in vitro by gene therapy (GMEB-SASSs). This proposal aims to perform pre-clinical testing in vitro and in vivo for the gene-modified SASS. We will also prepare the necessary documentation to undertake a clinical trial evaluating the treatment safety and efficacy for RDEB.
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/09/2020 |
28/02/2022 |
| 2020 |
Sandra Cohen (P) |
Hôpital Maisonneuve-Rosemont |
Avancement des essais cliniques |
Cohen |
Chercheur principal |
Sandra Cohen |
1 600 000 |
UM171-Expanded Cord Blood Grafts Offer Potential Cure for Very High-Risk Leukemia Patients |
Sang; leucémie |
|
Stem cell transplantation is one of the best therapies to cure blood cancers. Unfortunately, the risks of relapse (≈30%) and of dying from complications related to the transplant (also known as transplant related mortality ≈20%) remain high. Usually, patients receive bone marrow or blood stem cells from a related or unrelated compatible donor. Cord blood (CB) is an attractive alternative stem cell source due to its unique properties, including low risk of chronic graft-versus-host disease (GVHD) and relapse. A lower risk of chronic GVHD is very important as it is the major determinant of long-term quality of life after a transplant. However, these advantages of CB transplants are offset by the limited cell dose (i.e. small cords), which results in delayed recovery of blood counts, increased infections, prolonged hospitalization and early mortality. We have now completed a first clinical trial to test 2 Canadian discoveries, the UM171 small molecule developed in G. Sauvageau and A. Marinier’s laboratories (University of Montreal) and an optimized culture system from P. Zandstra’s laboratory (University of British Columbia). Combined, these ground-breaking technologies increase the number of stem cells in CB and were able to dramatically reduce transplant related mortality (<5%) with a very low risk of chronic GVHD. Most relevant to this grant, we also noticed a very low risk of blood cancer relapse in patients who had diseases with a very high risk of recurrence.
We now seek financial support to treat patients in a new trial to confirm that indeed UM171 CB has a potent anti-leukemia effect. For this we propose to recruit 20 very high risk acute leukemia/preleukemia patients (expected cure rate with standard transplant ≈20%) and compare them to historical control patients transplanted with similar high-risk disease. For this, we have brought together a Canadian multidisciplinary team with state-of-the-art expertise in stem cell biology, immunology, bioengineering, cell therapy, statistics and clinical transplantation. Using UM171-expanded CB grafts, we expect a cure rate of at least 50%, more than doubling the current expected results. This could represent a real breakthrough treatment for these mostly uncurable patients. |
01/01/2020 |
31/01/2022 |
| 2020 |
Veronique Moulin (P) |
Université Laval |
Avancement des essais cliniques |
Moulin |
Chercheur principal |
Veronique Moulin |
670 645 |
Self-Assembly Skin Substitutes (SASS) for the treatment of acute wounds of Canadian burn patients |
Brûlure cutanée, brûlures cutanées, brûlures de la peau |
|
The treatment of burn wounds is based on skin autografts. When the surface that needs to be covered is superior to 50% of the total body surface area, the treatment with autografts becomes strategic, the extent of the burns reducing the donor sites availability. With the tissue engineering method developed in our lab, autologous Self-Assembly Skin Substitutes (SASS) can be produced from only a small skin biopsy and could permanently cover all the patient wounds. Thanks to the Special Access Program of Health Canada, 14 patients have already been treated with very good results. This early phase clinical trial has now been accepted by Health Canada and few patients have been treated in Quebec Province. This project will allow to extend the trial to burn units in the rest of Canada. The aim of this trial is to evaluate this novel therapeutic approach, treating 17 patients to help skin regeneration. We plan to recruit at least 7 patients during the 2 next years and evaluate graft take and the post-grafting scar aspect during 2 to 3 years. Our aim is to treat majority of Canadian patients that have been burned on more than 50% of their body during the 2 years to come. To reach this goal, we will collaborate with the Canadian surgeons that are dedicated to the burn patient treatment. We speculate that SASS treatment will have economic and social benefits as our preliminary results have demonstrated that treatment decreases the morbidity generated by the standard treatment (decreasing further surgery needs and pain of the patients) and improves the quality of the post-burn scars.
Our interdisciplinary team is composed of four internationally known researchers in regenerative medicine from two universities and of plastic surgeons working in the major Canadian burn unit sites. Manufacturing SASS in Tissue processing centre built and directed by our team, we are the only Canadian team dedicated to the reconstruction of organized tissues to treat patients. At the end of the clinical trial and acceptance by Health Canada, we will be the first place in Canada to routinely treat patients with autologous reconstructed skin. |
01/01/2020 |
31/01/2022 |
| 2020 |
Bernard Thébaud (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Avancement des essais cliniques |
Thébaud |
Chercheur principal |
Bernard Thébaud |
638 150 |
HULC-I: Helping Underdeveloped Lungs with mesenchymal stromal Cells – A phase I trial |
Poumon, poumons |
|
Extreme prematurity is the main cause of death in children below 5 years of age. The most severe complication is bronchopulmonary dysplasia (BPD), a chronic lung disease that follows ventilator and oxygen treatment for acute failure to breathe. BPD also leads to brain damage and blindness. Currently, there is no treatment for BPD. Because these injuries occur in developing organs, consequences are life-long and carry a high economic burden. Thus, effective interventions at this stage of life provide exceptional value.
Our group was the first to demonstrate that umbilical cord-derived mesenchymal stromal cells (uc-MSCs) repair neonatal lung injury in experimental models. We then pioneered several innovations enabling this world’s first clinical trial: (1) a highly efficient, high yield, low passage, GMP clinical-grade uc-MSC product; (2) a novel team science approach (INCuBATOR: Innovative-Neonatal-CellUlar-therapies-for-BPD-Accelerating-Translation-Of-Research) to enhance clinical translation success through rigorous, evidence-based processes mitigating the potential high-risk nature of cell therapy in newborns. Thus, we created a strong, multidisciplinary, well-attuned, international team with complementary expertise to deliver on this research.
HULC-I is a Phase I, dose-escalation trial to determine the safety and feasibility of intravenous injection of allogeneic uc-MSCs for extreme preterm infants at high risk of developing BPD. The study includes an observational control group (n=12) and an interventional group (n=9). Our multi-disciplinary team has extensive experience in stem cell biology/manufacturing, clinical trials, health psychology and economics to ensure the success of this trial. The deliverables are to provide evidence for a larger, Phase II Canadian multi-centre trial, to determine the safety and efficacy of uc-MSCs. Ultimately, HULC-I will provide a potential breakthrough therapy to improve the outcome of extreme preterm babies in Canada and world-wide.
HULC-I will also deliver social and economic benefits by providing a new workforce of HQP and developing novel commercial entities. Our partner at the Technische Universität Dresden holds a patent for the uc-MSC product that is currently being internationalized in Europe, USA and Canada. The spin-off MDTB Cells GmbH will further develop and distribute a novel, high quality uc-derived MSC product with plans to establish a spin-off in Canada to facilitate operations in North America. |
01/01/2020 |
31/01/2022 |
| 2020 |
Lucie Germain (P) |
Université Laval |
Avancement des essais cliniques |
Germain |
Chercheur principal |
Lucie Germain |
500 000 |
Cultured epithelial corneal autografts for the treatment of Canadians with limbal stem cell deficiency |
Oculaire, déficit en cellules souches limbiques |
|
Limbal stem cell deficiency (LSCD) is a severe disease caused by damage or depletion of stem cells in the corneal limbal region of the eye following trauma or disease. The LOEX/CHU de Québec, a leader in autologous epithelium therapy using cultured stem cells, has performed the first clinical trial in Canada offering cultured epithelial corneal autograft (CECA) as a treatment for the LSCD.
The objective of the present proposal is to develop a multicenter clinical trial (Quebec, Montreal and Toronto) to recruit a greater number of LSCD patients for the collection of safety data on the CECA graft, but with a primary endpoint focused on efficacy. Therefore, we expect to: i) establish and organize new clinical sites, which involves the training of new cornea specialists for CECA grafting, ii) recruit and treat 34 adult patients and 5 minor patients, and iii) educate and advise Canadian ophthalmologists on this new therapeutic alternative now available in Canada.
Following successful clinical testing, this trial will provide clinical proof-of-concept for a safe and effective stem cell-based therapy accessible to Canadian ophthalmologists and their patients for the treatment of LSCD. Without treatment, LSCD results in severe visual impairments which impacts on the quality of life of patients and their families. LSCD is a rare disease that affects patients' ability of the patient to work, drive and conduct their daily activities. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving vision in their affected eye.
Our interdisciplinary team brings together three fundamental investigators, including two experts in tissue-engineering and an expert in ethical/legal issues, three clinician ophtalmologists, one pathologist, many research professionals experienced in the clinical translation of tissue engineering products and a patient representative. The LOEX is equipped with clean rooms and has been producing CECA since 2012. Thus, our research group has the infrastructure, expertise and knowledge to ensure the success of the project. |
01/01/2020 |
31/01/2022 |
| 2020 |
Yun Li (C) |
Hospital for Sick Children |
L’intervention de recherche rapide du RCS contre la COVID-19 |
Muffat |
Cochercheur |
Yun Li, Julien Muffat |
90 000 |
Investigating the role of inflammatory responses in neurological effects of COVID-19, using patient-derived stem cell models |
COVID-19, neural, neuronale |
|
The COVID-19 pandemic, due to the coronavirus SARS-CoV-2, is taking an enormous toll on populations worldwide. The primary presentation is pneumonia, yet the disease clearly affects multiple organs, often culminating in liver and kidney damage. Severity of the disease may often find its roots in an inappropriately intense and prolonged innate immune response, a so-called cytokine storm, driven by innate immune cells (macrophages). Strikingly, many patients report sensory symptoms, such as loss of smell and taste, pains, visual disturbances, and headaches. These indicate that the virus may target the brain. The brain harbors a population of prototypic tissue-resident innate immune cells, the microglia. In the brain, these cells are normally protected from peripheral insults. However, they will respond to inflammatory stimuli that do reach them, and are known to be the target of neuro-invasive viruses. We propose to investigate the neuro-invasive potential of SARS-CoV-2, with an emphasis on the role of resident innate immune cells in mediating the injury. Given the species restriction of SARS-CoV-2, we will work with a set of novel human tissue culture models that we uniquely developed to investigate inflammatory etiologies of neurological diseases. We previously successfully and rapidly deployed similar technologies during the Zika epidemic. We will assess infection parameters and cellular responses in brain cells derived from patient stem cells. Working with brain-resident immune cells will shed light on the interaction of SARS-CoV-2 with similar cellular targets in other organs, such as the lungs. We will study the virus’ ability to enter, replicate, kill the cells or trigger unchecked inflammation. We will dissect the host machinery involved in these responses by identifying protective or damaging mutations, generated using CRISPR technology for every gene in those cells. Our team has the technical know-how and access to all resources needed to deliver rapidly on our plans. |
17/04/2020 |
16/04/2021 |
| 2020 |
Julien Muffat (P) |
Hospital for Sick Children |
L’intervention de recherche rapide du RCS contre la COVID-19 |
Muffat |
Chercheur principal |
Yun Li, Julien Muffat |
90 000 |
Investigating the role of inflammatory responses in neurological effects of COVID-19, using patient-derived stem cell models |
COVID-19, neural, neuronale |
|
The COVID-19 pandemic, due to the coronavirus SARS-CoV-2, is taking an enormous toll on populations worldwide. The primary presentation is pneumonia, yet the disease clearly affects multiple organs, often culminating in liver and kidney damage. Severity of the disease may often find its roots in an inappropriately intense and prolonged innate immune response, a so-called cytokine storm, driven by innate immune cells (macrophages). Strikingly, many patients report sensory symptoms, such as loss of smell and taste, pains, visual disturbances, and headaches. These indicate that the virus may target the brain. The brain harbors a population of prototypic tissue-resident innate immune cells, the microglia. In the brain, these cells are normally protected from peripheral insults. However, they will respond to inflammatory stimuli that do reach them, and are known to be the target of neuro-invasive viruses. We propose to investigate the neuro-invasive potential of SARS-CoV-2, with an emphasis on the role of resident innate immune cells in mediating the injury. Given the species restriction of SARS-CoV-2, we will work with a set of novel human tissue culture models that we uniquely developed to investigate inflammatory etiologies of neurological diseases. We previously successfully and rapidly deployed similar technologies during the Zika epidemic. We will assess infection parameters and cellular responses in brain cells derived from patient stem cells. Working with brain-resident immune cells will shed light on the interaction of SARS-CoV-2 with similar cellular targets in other organs, such as the lungs. We will study the virus’ ability to enter, replicate, kill the cells or trigger unchecked inflammation. We will dissect the host machinery involved in these responses by identifying protective or damaging mutations, generated using CRISPR technology for every gene in those cells. Our team has the technical know-how and access to all resources needed to deliver rapidly on our plans. |
17/04/2020 |
16/04/2021 |
| 2020 |
Amy Wong (C) |
Hospital for Sick Children |
L’intervention de recherche rapide du RCS contre la COVID-19 |
Stanford |
Cochercheur |
William Stanford, Amy Wong |
77 120 |
Identifying and targeting pulmonary and immune mechanisms in COVID-19 using human stem cell derived lineages |
COVID-19, poumon, poumons, pulmonaire, vasculaire |
|
Understanding why some COVID-19 patients develop acute respiratory distress syndrome (ARDS) that drives morbidity and mortality is unclear but is urgently needed to determine which patients should be treated early and develop therapeutic interventions to save lives. The two known comorbidities – hypertension and diabetes – associated with severe COVID-19 suggests a vascular pathology. In fact, in addition to the respiratory epithelia, the lung vasculature expresses high levels of angiotensin converting enzyme-2 (ACE-2), the receptor that SARS-CoV-2 uses to infect cells. Additionally, it appears from emerging studies that a myeloid-dominant cytokine storm contributes to lung tissue injury in COVID-19 ARDS.
With our partners at BioSymetrics, we will leverage our team’s expertise in lung and stem cell biology, disease modeling, immunology, bioengineering, drug screening and development, and infectious disease to dissect underlying molecular and cellular mechanisms driving disease severity and screen for disease modifying drugs. To maximize translational impact, our team’s unique approach uses human pluripotent stem cells to generate ACE2-expressing respiratory epithelia grown in a tissue-mimetic air liquid interface and vascular cells grown in a lung-mimetic hydrogel to analyze infectivity and cellular and molecular behaviour in response to SARS-CoV-2. Moreover, we will perform single cell RNA-seq analyses and co-culture studies with control and infected peripheral blood derived myeloid cells to model the altered lung epithelia, vascular, and immune responses in COVID-19. These mechanistic studies will be mined to discover putative biomarkers that identify patients likely to require intensive care so that acute care may be started early to prevent the need for intensive care. Finally, using a novel ACE2 activity high content imaging assay, we will implement a Health Canada/FDA approved drug repurposing screen to identify therapeutics to reduce disease severity. |
17/04/2020 |
16/04/2021 |
| 2020 |
William Stanford (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
L’intervention de recherche rapide du RCS contre la COVID-19 |
Stanford |
Chercheur principal |
William Stanford, Amy Wong |
118 750 |
Identifying and targeting pulmonary and immune mechanisms in COVID-19 using human stem cell derived lineages |
COVID-19, poumon, poumons, pulmonaire, vasculaire |
|
Understanding why some COVID-19 patients develop acute respiratory distress syndrome (ARDS) that drives morbidity and mortality is unclear but is urgently needed to determine which patients should be treated early and develop therapeutic interventions to save lives. The two known comorbidities – hypertension and diabetes – associated with severe COVID-19 suggests a vascular pathology. In fact, in addition to the respiratory epithelia, the lung vasculature expresses high levels of angiotensin converting enzyme-2 (ACE-2), the receptor that SARS-CoV-2 uses to infect cells. Additionally, it appears from emerging studies that a myeloid-dominant cytokine storm contributes to lung tissue injury in COVID-19 ARDS.
With our partners at BioSymetrics, we will leverage our team’s expertise in lung and stem cell biology, disease modeling, immunology, bioengineering, drug screening and development, and infectious disease to dissect underlying molecular and cellular mechanisms driving disease severity and screen for disease modifying drugs. To maximize translational impact, our team’s unique approach uses human pluripotent stem cells to generate ACE2-expressing respiratory epithelia grown in a tissue-mimetic air liquid interface and vascular cells grown in a lung-mimetic hydrogel to analyze infectivity and cellular and molecular behaviour in response to SARS-CoV-2. Moreover, we will perform single cell RNA-seq analyses and co-culture studies with control and infected peripheral blood derived myeloid cells to model the altered lung epithelia, vascular, and immune responses in COVID-19. These mechanistic studies will be mined to discover putative biomarkers that identify patients likely to require intensive care so that acute care may be started early to prevent the need for intensive care. Finally, using a novel ACE2 activity high content imaging assay, we will implement a Health Canada/FDA approved drug repurposing screen to identify therapeutics to reduce disease severity. |
17/04/2020 |
16/04/2021 |
| 2020 |
Duncan Stewart (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
L’intervention de recherche rapide du RCS contre la COVID-19 |
Stewart |
Chercheur principal |
Duncan Stewart |
300 000 |
Cellular Immuno-Therapy for COVID-19 induced Acute Respiratory Distress Syndrome: the CIRCA-19 Trial |
COVID-19, cellules stromales mésenchymateuses, CSM |
|
The clinical picture of the novel corona virus 2 (SARS-CoV-2) disease (COVID-19) is rapidly evolving. Although 80% of infections may be mild, up to 25% of all patients admitted to hospital require admission to the intensive care unit, and as many as 40% will progress to develop severe problems breathing due to the acute respiratory distress syndrome (ARDS). This often requires mechanical ventilation, with a 50% risk of mortality. Researchers at the Ottawa Hospital Research Institute (OHRI) have been studying the potential therapeutic role of mesenchymal stromal/stem cells, or MSCs, for the treatment of ARDS for over a decade. This has led to the world’s first clinical trial using MSC therapy for patients with severe infections (sepsis) which often are associated with ARDS. This trial demonstrated tolerability, and some signs of efficacy. In addition, we have established expertise in producing clinical-grade MSCs and have received approval from Health Canada for the use of MSCs in 3 different clinical studies. Here, we propose a series of trials to allow us to rapidly initiate a clinical study to establish feasibility and safety of MSCs treatment in patients with COVID-19 related ARDS. In total, 27 patients will be entered into three sequential trial. The first trial, called the ‘Vanguard’ study, is designed to determine the optimal of dose of bone marrow-derived MSCs to be used for these very sick patients. The next two trials will use this same optimal dose of cells, but will administer MSCs derived from the umbilical cord, which is an abundant and readily available source. In this way we will confirm the safety of the use of umbilical cord MSCs and obtain preliminary information about their potential benefits in the treatment of this often lethal disease. |
17/04/2020 |
16/04/2021 |
| 2020 |
Mannix Auger-Messier (C) |
Université de Sherbrooke |
Recherche innovante |
Bentzinger |
Cochercheur |
Florian Bentzinger, Ubaka Ogbogu, Eric Marsault, Pierre-Luc Boudreault, Penney Gilbert, Mannix Auger-Messier |
32 000 |
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy |
Muscle, muscles |
Rare disease status |
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke. |
01/01/2020 |
31/01/2022 |
| 2020 |
Penney Gilbert (C) |
University of Toronto |
Recherche innovante |
Bentzinger |
Cochercheur |
Florian Bentzinger, Ubaka Ogbogu, Eric Marsault, Pierre-Luc Boudreault, Penney Gilbert, Mannix Auger-Messier |
62 000 |
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy |
Muscle, muscles |
Rare disease status |
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke. |
01/01/2020 |
31/01/2022 |
| 2020 |
Eric Marsault (C) |
Université de Sherbrooke |
Recherche innovante |
Bentzinger |
Cochercheur |
Florian Bentzinger, Ubaka Ogbogu, Eric Marsault, Pierre-Luc Boudreault, Penney Gilbert, Mannix Auger-Messier |
82 000 |
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy |
Muscle, muscles |
Rare disease status |
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke. |
01/01/2020 |
31/01/2022 |
| 2020 |
Pierre-Luc Boudreault (C) |
Université de Sherbrooke |
Recherche innovante |
Bentzinger |
Cochercheur |
Florian Bentzinger, Ubaka Ogbogu, Eric Marsault, Pierre-Luc Boudreault, Penney Gilbert, Mannix Auger-Messier |
49 200 |
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy |
Muscle, muscles |
Rare disease status |
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke. |
01/01/2020 |
31/01/2022 |
| 2020 |
Ubaka Ogbogu (C) |
University of Alberta |
Recherche innovante |
Bentzinger |
Cochercheur |
Florian Bentzinger, Ubaka Ogbogu, Eric Marsault, Pierre-Luc Boudreault, Penney Gilbert, Mannix Auger-Messier |
42 000 |
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy |
Muscle, muscles |
Rare disease status |
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke. |
01/01/2020 |
31/01/2022 |
| 2020 |
Florian Bentzinger (P) |
Université de Sherbrooke |
Recherche innovante |
Bentzinger |
Chercheur principal |
Florian Bentzinger, Ubaka Ogbogu, Eric Marsault, Pierre-Luc Boudreault, Penney Gilbert, Mannix Auger-Messier |
112 000 |
Targeting Endogenous Repair: A Novel Mutation Independent Pharmacological Approach for the Treatment of Muscular Dystrophy |
Muscle, muscles |
Rare disease status |
Defects in the regenerative function of muscle stem cells (MuSCs) have been shown to contribute to the pathogenesis of muscular dystrophy, a group of rare and uncurable diseases that often affects young children. Using a preclinical model of merosin-deficient congenital muscular dystrophy type 1A (MDC1A) that is characterized by severe regenerative failure, we investigated the effectivity of a novel class of compounds derived from a circulating hormone that can stimulate MuSC function. We observed that these molecules significantly ameliorate disease progression. Systemic delivery of our compounds boosts MuSC numbers, promotes repair of the diseased muscle, and restores force generation in the absence of adverse cardio-vascular effects. Notably, the treatment increases life-expectancy, makes the diseased muscles stronger, and significantly improves motor function.
In our proposal we aim to further develop this discovery towards the clinics. Across three Canadian provinces, we bring together internationally renowned experts from the fields of regenerative medicine, medicinal chemistry, bioengineering, cardiovascular research, and law and ethics. The proposed research is highly translational and would establish a first-in-its-class "endogenous repair therapeutic" for muscle disease. Our work will (I) lead to the identification of compounds with improved efficacy, will (II) test the off-label use of an approved drug that stimulates the same molecular target, and will (III) lay the foundation for progression towards clinical trials.
Importantly, endogenous repair therapeutics are effective independent of underlying genetic mutations Thus, we expect our novel therapeutic approach to have broad impact on several different types of muscular dystrophy. A stem cell targeted therapeutic agent boosting skeletal muscle repair represents an unprecedented and highly disruptive discovery that pioneers a novel class of therapeutics with the potential to have a dramatic impact in the field of regenerative medicine. Our partners for this project are the Institute of Biomaterials and Biomedical Engineering (IBBME) of the University of Toronto, and the Centre de recherche du CHU Sherbrooke (CRC), the Faculté de médecine et des sciences de la santé (FMSS) and the Institut de pharmacologie de Sherbrooke (IPS) of the Université de Sherbrooke. |
01/01/2020 |
31/01/2022 |
| 2020 |
Jodi Warman (C) |
Université d’Ottawa |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Khacho |
Cochercheur |
Mireille Khacho, Jodi Warman |
20 300 |
Mitochondrial dynamics as a therapeutic target for muscle stem cells in muscle wasting diseases |
Muscle, muscles |
Rare disease status |
An estimated 4 million Canadians currently suffer from muscle wasting conditions, manifesting as loss of muscle mass and function. Muscle wasting is the most significant cause of disability in the aging population and individuals with muscle degenerative diseases, including muscular dystrophies, myopathies and aging. The decline in muscle function affects mobility, voluntary function and quality of life, often leading to institutionalization and mortality. This imposes a dramatic burden on individuals and society, costing Canadians several billions of dollars per year. Thus, there is a pressing need for the development of preventative and therapeutic strategies targeting muscle wasting. For many years, muscle wasting was thought to be only a problem of the myofibers, yet recent evidence shows that muscle stem cell (MuSC) dysfunction plays a significant role. Adult skeletal muscle normally has a high regenerative capacity, however, within the context of muscle wasting MuSCs are depleted and muscle regeneration is impaired. Currently, the reason for MuSC depletion is unclear and thus there are no therapies targeting their restoration. Understanding the underlying etiological factors leading to MuSC depletion is instrumental in identifying novel approaches to restore muscle repair and function. Our recent studies were the first to uncovered that dysregulation of mitochondrial dynamics and function, as observed in muscle wasting, impairs stem cell longevity and regenerative capacity. The overarching goal of this proposal is to restore MuSC number and function and promote muscle repair in aging and muscle wasting diseases. The combination of our proposed animal and human studies of muscle stem cells will provide novel therapeutic options using pharmaceutical and supplementation strategies. Importantly, this could have immediate translational potential to a clinical environment to improve muscle function and quality of life in patients. |
01/09/2020 |
28/02/2022 |
| 2020 |
Mireille Khacho (P) |
Université d’Ottawa |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Khacho |
Chercheur principal |
Mireille Khacho, Jodi Warman |
129 700 |
Mitochondrial dynamics as a therapeutic target for muscle stem cells in muscle wasting diseases |
Muscle, muscles; divers |
Rare disease status |
An estimated 4 million Canadians currently suffer from muscle wasting conditions, manifesting as loss of muscle mass and function. Muscle wasting is the most significant cause of disability in the aging population and individuals with muscle degenerative diseases, including muscular dystrophies, myopathies and aging. The decline in muscle function affects mobility, voluntary function and quality of life, often leading to institutionalization and mortality. This imposes a dramatic burden on individuals and society, costing Canadians several billions of dollars per year. Thus, there is a pressing need for the development of preventative and therapeutic strategies targeting muscle wasting. For many years, muscle wasting was thought to be only a problem of the myofibers, yet recent evidence shows that muscle stem cell (MuSC) dysfunction plays a significant role. Adult skeletal muscle normally has a high regenerative capacity, however, within the context of muscle wasting MuSCs are depleted and muscle regeneration is impaired. Currently, the reason for MuSC depletion is unclear and thus there are no therapies targeting their restoration. Understanding the underlying etiological factors leading to MuSC depletion is instrumental in identifying novel approaches to restore muscle repair and function. Our recent studies were the first to uncovered that dysregulation of mitochondrial dynamics and function, as observed in muscle wasting, impairs stem cell longevity and regenerative capacity. The overarching goal of this proposal is to restore MuSC number and function and promote muscle repair in aging and muscle wasting diseases. The combination of our proposed animal and human studies of muscle stem cells will provide novel therapeutic options using pharmaceutical and supplementation strategies. Importantly, this could have immediate translational potential to a clinical environment to improve muscle function and quality of life in patients. |
01/09/2020 |
28/02/2022 |
| 2020 |
Yun Li (P) |
Hospital for Sick Children |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Li |
Chercheur principal |
Yun Li |
150 000 |
Engineering an organoid model of the hippocampal neurogenic niche for basic and translational research |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
The hippocampus is a unique structure in the human brain that contains a long-lasting neurogenic niche. During fetal development, neurons are generated by radial glia (RG), the bona fide neural stem cells of the brain. While RG in most other regions of the human brain are depleted prior to birth, some RG in the fetal hippocampus remain undifferentiated and persist for decades after birth. As a result, the hippocampus is one of the only regions of the brain where new neurons are born throughout life. However, our knowledge of the fetal hippocampal neurogenic niche is extremely limited, because of the inaccessible nature of the human fetal brain. It has been hypothesized that the long-lasting nature of the hippocampal RG critically depends on their ability to enter quiescence. Disruption of this process during fetal development likely has profound consequences on the capacity of postnatal and adult hippocampal neurogenesis. Addressing these important unknowns requires experimental models of the developing human brain, and genetic tools to manipulate the human genome, prerequisites unattainable until recently.
In the current proposal, we seek to engineer a novel organoid model of the human hippocampal neurogenic niche, to study normal and pathological development. Combining breakthrough technologies in human pluripotent stem cells (hPSCs), genome editing, and 3D organoids, my lab has recently reported that human brain development and diseases could be modeled in vitro. In unpublished results, we have created a suite of genetically engineered hPSCs to label, manipulate, and ablate hippocampal RG. These expertise and genetic tools put us at a uniquely advantageous position to carry out the proposed research. Our work will establish a significant long-term resource for studying human hippocampal neurogenesis in health and disease. |
01/09/2020 |
28/02/2022 |
| 2020 |
Stephanie Protze (P) |
University Health Network |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Protze |
Chercheur principal |
Stephanie Protze, Zachary Laksman |
127 400 |
Developing stem cell-based biological pacemakers for patients with sick sinus syndrome |
Cardiaque; maladie du sinus, dysfonctionnement du nœud sinusal, maladie de l’oreillette |
Rare disease status |
The human heartbeat is controlled by the primary pacemaker known as the sinoatrial node (SAN). Failure of the SAN, due to diseases or aging, causes a life-threatening slow heartbeat and needs to be treated by implantation of an electronic pacemaker. Approximately 21,000 Canadians receive an electronic pacemaker every year, a number that is steadily increasing with an aging population. The treatment with electronic pacemakers has a couple of disadvantages such as the need for surgical battery replacements, the lack of autonomic responsiveness, and the risk of complications such as infection of the leads and pacing-induced heart failure.
In this project we aim to develop a stem cell-derived biological pacemaker that could overcome these disadvantages by replacing the damaged SAN with new functional pacemaker cells. We have already established a method for the generation of stem cell-derived SAN pacemaker cells. A large number of these SAN cells are required to create a biological pacemaker. This can be easiest accomplished by a positive selection process. As part of this project we will validate a novel cell surface marker that we have recently discovered to be present on SAN pacemaker cells. We will test the utility of this marker to isolate large numbers of SAN pacemaker cells from differentiated stem cell cultures. In addition, we will establish a novel animal model of SAN disease and provide proof of concept that these stem cell-derived SAN pacemaker cells can function as a biological pacemaker in this model.
To successfully carry out this translational project, we have put together an interdisciplinary team including: Dr. Laksman (UBC, Vancouver), a clinician scientist; Dr. Laflamme (UHN, Toronto), an expert in cell therapies for the heart; Dr. Bader (UofT, Toronto), a computational biologist; and Dr. Efimov (GWU, Washington, US), a pioneer of experimental electrophysiology with extensive expertise in heart rhythm disorders; and myself, Dr. Protze (UHN, Toronto), an early career investigator with expertise in developmental and stem cell biology.
Taken together, our team will advance the development of biological pacemakers that represent a possible cure, rather than a treatment, for patients with pacemaker diseases in Canada and worldwide. |
01/09/2020 |
28/02/2022 |
| 2020 |
Zachary Laksman (C) |
University of British Columbia |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Protze |
Cochercheur |
Stephanie Protze, Zachary Laksman |
22 600 |
Developing stem cell-based biological pacemakers for patients with sick sinus syndrome |
Cardiaque |
Rare disease status |
The human heartbeat is controlled by the primary pacemaker known as the sinoatrial node (SAN). Failure of the SAN, due to diseases or aging, causes a life-threatening slow heartbeat and needs to be treated by implantation of an electronic pacemaker. Approximately 21,000 Canadians receive an electronic pacemaker every year, a number that is steadily increasing with an aging population. The treatment with electronic pacemakers has a couple of disadvantages such as the need for surgical battery replacements, the lack of autonomic responsiveness, and the risk of complications such as infection of the leads and pacing-induced heart failure.
In this project we aim to develop a stem cell-derived biological pacemaker that could overcome these disadvantages by replacing the damaged SAN with new functional pacemaker cells. We have already established a method for the generation of stem cell-derived SAN pacemaker cells. A large number of these SAN cells are required to create a biological pacemaker. This can be easiest accomplished by a positive selection process. As part of this project we will validate a novel cell surface marker that we have recently discovered to be present on SAN pacemaker cells. We will test the utility of this marker to isolate large numbers of SAN pacemaker cells from differentiated stem cell cultures. In addition, we will establish a novel animal model of SAN disease and provide proof of concept that these stem cell-derived SAN pacemaker cells can function as a biological pacemaker in this model.
To successfully carry out this translational project, we have put together an interdisciplinary team including: Dr. Laksman (UBC, Vancouver), a clinician scientist; Dr. Laflamme (UHN, Toronto), an expert in cell therapies for the heart; Dr. Bader (UofT, Toronto), a computational biologist; and Dr. Efimov (GWU, Washington, US), a pioneer of experimental electrophysiology with extensive expertise in heart rhythm disorders; and myself, Dr. Protze (UHN, Toronto), an early career investigator with expertise in developmental and stem cell biology.
Taken together, our team will advance the development of biological pacemakers that represent a possible cure, rather than a treatment, for patients with pacemaker diseases in Canada and worldwide. |
01/09/2020 |
28/02/2022 |
| 2020 |
Jo Stratton (P) |
Université McGill |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Stratton |
Chercheur principal |
Jo Stratton |
150 000 |
Human iPSC ependymal cells: An innovative model to study human brain in health and disease |
Neural, neuronal, neurale, neuronale, neurales, neuronales |
|
The major technological breakthrough of the description of “Yamanaka factors” enables the reprogramming of human cells into pluripotent stem cells appropriate for deriving a diversity of human cells that have previously been inaccessible for study. This includes the study of brain cells, such as neurons and several glia cell types, that are notoriously difficult to access. The ependymal cell – the brain’s epithelial barrier cell, lines the entire ventricular system and is critically understudied largely due to a lack of reliable cellular models for their study. Ependymal cells regulate cerebrospinal fluid (CSF) circulation; and over the last decade, their role in the maintenance of CSF homeostasis is becoming much more appreciated. There is an overwhelming number of neurological conditions and diseases that are subject to ependymal cell abnormalities, which can subsequently interfere with developmental processes, regenerative mechanisms and contribute to disease progression.
Developing a robust method for generating ependymal cell cultures would not only greatly benefit my research program but would also have a wider impact on the research community, given no such method currently exists. Our objective is to use human iPSCs to develop a robust method for the routine culturing of human ependymal cells. In the process of developing this translational method, we will gain a greater understanding of the developmental timelines of human ependymal cells and apply this knowledge to better inform their regenerative potential and how they may become compromised in disease. We can use this system to understand how genes and environment interact in diseases impacting ependymal cells or impacted by ependymal cells - an accomplishment in both the fields of stem cell biology and ependymal cell biology. Ultimately, we will generate methodology that will be disseminated openly via Open-Access journals and at conferences. Along with our team of iPSC and glia experts, Drs Thomas Durcan and Luke Healy, as well as ependymal cell biologist, Jo Anne Stratton, we are well positioned to execute this project. Finally, the McGill Regenerative Network is an instrumental partner for this project, where they will support trainee stipend costs and provide network resources. |
01/09/2020 |
28/02/2022 |
| 2020 |
Amy Wong (P) |
Hospital for Sick Children |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Wong |
Chercheur principal |
Amy Wong |
150 000 |
Elucidating the role of CFTR in human fetal lung lineage development |
Poumon, poumons |
Rare disease status |
Cystic Fibrosis (CF) is a common genetic disease which causes difficulties in breathing, recurrent lung infections. Children under the age of 12 are not eligible for current treatments (at a cost of $300,000 CAD/year for a lifetime) aimed at targeting the main CF genetic mutation. This has been a large debate over the past few years with clinicians arguing for the early treatment of CF in children to mitigate the extent of lung damage caused by this progressively fatal disease. However, there has not been useful models to really understand the impact of CFTR functional correction in human fetuses, neonates, or young children, let alone understand the role of CFTR in normal lung development.
In 2012, I developed the first human lung in the petri dish derived solely from pluripotent stem cells. These stem cells when generated from individuals with CF enabled the use of an unlimited source of lung cells to better understand individual CF disease and personalized screens for therapeutic drugs. My lab has since expanded our stem cell-derived lung model repertoire to include fetal, immature and mature lungs derived from induced pluripotent stem cells. We have the unique models to understand how a defect in CFTR expression can impact normal development and long-term lung functions that impact therapy outcomes. We will do so my combining single cell technologies, mathematical modeling, stem cell and primary tissue models to address: 1) the origins and lineage relationship of cells expressing CFTR during development, 2) CFTR expression and function in normal lung development and, 3) the effects of CFTR mutation in lung lineage development. Our overarching goal is to understand the role of CFTR in early lung development and CF pathogenesis. Early treatment of CF lung disease will translate to meaningful therapeutic outcome that improves the health, economic and social welfare of the patient and benefits our Canadian healthcare system. |
01/09/2020 |
28/02/2022 |
| 2020 |
Natasha Chang (P) |
Université McGill |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Chang |
Chercheur principal |
Natasha Chang |
150 000 |
Targeting muscle stem cells to enhance endogenous repair in Duchenne muscular dystrophy |
Muscle, muscles; dystrophie musculaire de Duchenne, DMD |
Rare disease status |
Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effective cure for DMD. Recent studies have shown that muscle stem cells, which are adult stem cells responsible for muscle repair, are also affected in DMD. DMD muscle stem cells do not function as normal healthy muscle stem cells and their impairment plays a contributing role in disease progression. Current therapeutic strategies for muscular dystrophy do not address the deficiencies in muscle stem cell function. Here, we describe a novel approach to target muscle stem cells to mitigate the disease. We have found that a group of small molecule compounds known to have anti-tumorigenic properties that protect against muscle wasting have the ability to improve muscle differentiation, the process whereby muscle stem cells make mature muscle cells. This study investigates the use of these compounds to boost the regenerative capacity of muscle stem cells. We propose that enhancing muscle repair through the restoration of muscle stem cell function will improve muscle quality and strength in DMD. The findings from these studies will provide proof-of-concept validation to further develop these compounds for clinical use in DMD patients. This project is lead by Dr. Natasha Chang, an Assistant Professor at McGill University who specializes in muscle stem cell biology and muscle stem cell contributions to muscle pathologies. This project is supported by a multi-disciplinary team of investigators including Dr. Jerry Pelletier and Dr. Imed Gallouzi, experts on mRNA translation mechanisms and muscle wasting, as well as Dr. Gerald Pfeffer, who specializes in neuromuscular diseases. Moreover, this project is supported through generous support from McGill University, the McGill Regenerative Medicine Network, Muscular Dystrophy Canada, and Aurora Scientific Inc. |
01/09/2020 |
28/02/2022 |
| 2020 |
Kathleen Hodgkinson (C) |
Memorial University of Newfoundland |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Esseltine |
Cochercheur |
Jessica Esseltine, Kathleen Hodgkinson |
20 000 |
A personalized, translational approach to understanding inherited Arrhythmogenic Right Ventricular Cardiomyopathy in Newfoundland |
Cardiaque |
Rare disease status |
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart disease that can cause sudden death as its first symptom. It tragically shortens the lives of healthy young people, with men affected worse than women. 50% of ARVC men will die by age 40, and 80% by 50 (5% and 20% of women).
Genes are messages written in a DNA alphabet that build proteins. Proteins are the building blocks of the cells from which we are all made. A mistake in a gene can disrupt the protein causing serious disease. ARVC in Newfoundland is caused by a DNA spelling mistake in a gene called TMEM43. This mutation was discovered in Newfoundland. Men and women both inherit the TMEM43 gene mutation, and pass it on to 50% of their children. Thus, ARVC is known as “The Newfoundland curse”.
Although all people with the TMEM43 gene mutation will get ARVC, it is not the same severity in everyone. We know nothing about what this gene change does to heart cells. We do not know why women are protected compared to men. We do not know why some dies suddenly or need a heart transplant, while others live relatively normal lives.
We have a dedicated group of families invested in helping with our research. We will collect skin samples from affected and unaffected family members and ‘reprogram’ their skin cells into induced pluripotent stem cells (iPSC). These iPSCs can become any cell type. So we can take skin cells and turn them into beating heart cells. We can then investigate how ARVC heart cells are different than their unaffected siblings. We can “repair” the DNA in these cells using CRISPR-Cas9 technology. The large families mean we can access subjects with severe forms of ARVC, and less severe forms, and access their gene negative brothers and sisters as controls.
Although concentrated within NL, ARVC caused by this mutation is seen worldwide. This research proposal will allow us to understand basic ARVC biology, which may lead to new therapies based on understanding the causes of the variation in disease presentation we see, leading to true precision medicine. |
01/09/2020 |
28/02/2022 |
| 2020 |
Jessica Esseltine (P) |
Memorial University of Newfoundland |
Programme de soutien à la recherche innovante pour les chercheurs en début de carrière |
Esseltine |
Chercheur principal |
Jessica Esseltine, Kathleen Hodgkinson |
130 000 |
A personalized, translational approach to understanding inherited Arrhythmogenic Right Ventricular Cardiomyopathy in Newfoundland |
Cardiaque; cardiomyopathie ventriculaire droite arythmogène, CVDA |
Rare disease status |
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart disease that can cause sudden death as its first symptom. It tragically shortens the lives of healthy young people, with men affected worse than women. 50% of ARVC men will die by age 40, and 80% by 50 (5% and 20% of women).
Genes are messages written in a DNA alphabet that build proteins. Proteins are the building blocks of the cells from which we are all made. A mistake in a gene can disrupt the protein causing serious disease. ARVC in Newfoundland is caused by a DNA spelling mistake in a gene called TMEM43. This mutation was discovered in Newfoundland. Men and women both inherit the TMEM43 gene mutation, and pass it on to 50% of their children. Thus, ARVC is known as “The Newfoundland curse”.
Although all people with the TMEM43 gene mutation will get ARVC, it is not the same severity in everyone. We know nothing about what this gene change does to heart cells. We do not know why women are protected compared to men. We do not know why some dies suddenly or need a heart transplant, while others live relatively normal lives.
We have a dedicated group of families invested in helping with our research. We will collect skin samples from affected and unaffected family members and ‘reprogram’ their skin cells into induced pluripotent stem cells (iPSC). These iPSCs can become any cell type. So we can take skin cells and turn them into beating heart cells. We can then investigate how ARVC heart cells are different than their unaffected siblings. We can “repair” the DNA in these cells using CRISPR-Cas9 technology. The large families mean we can access subjects with severe forms of ARVC, and less severe forms, and access their gene negative brothers and sisters as controls.
Although concentrated within NL, ARVC caused by this mutation is seen worldwide. This research proposal will allow us to understand basic ARVC biology, which may lead to new therapies based on understanding the causes of the variation in disease presentation we see, leading to true precision medicine. |
01/09/2020 |
28/02/2022 |
| 2020 |
Jean-François Bouchard (C) |
Université de Montréal |
Subventions de soutien aux partenariats biotechnologiques |
Bernier |
Cochercheur |
Gilbert Bernier, May Griffith, Jean-François Bouchard |
66 000 |
Photoreceptor transplantation for the treatment of retinal degenerative diseases |
Oculaire |
|
Retinal degenerative diseases including age-related macular degeneration is the leading cause of Canadian and global vision loss after cataracts; and there are no reliable treatments. Our project aimed at photoreceptor stem cell transplantation therapy is unique Canadian and is developed by our internationally renowned interdisciplinary team with expertise in stem cell and biomaterials engineering, vision function analysis and retinal transplantation surgery. The use of novel anti-angiogenic and pro-survival agents in photoreceptor cell transplantation therapy is of interest to academia, while the resulting intellectual property is of commercial significance. Current objectives for this grant are to implement a proof-of-principle of macular transplantation therapy in non-human primates, confirm safety of the cell transplantation therapy, and validate the use of a universal donor induced pluripotent cell line for generation of therapeutic cone photoreceptors. Deliverables include the demonstration of functional vision restoration in a non-human primate model of macular degeneration, and confirmation of the functionality and non-immunogenic nature of our universal donor cell line. We anticipate that successful completion of this proposed project will help restoring or improving central vision in patients suffering from late-stage RP, Stargardt’s disease, cone dystrophies, cone/rod dystrophies and age-related macular degeneration. The clinical, social and economic impacts of this treatment is thus possibly considerable for Canadians and patients abroad. The ownership of the technology by a Canadian entity is also economically beneficial for Canadians and Canada in general. Importantly, the treatment should be widely accessible following the use of a universal donor cell line, allowing treatment of all patients at a predicted low cost. Our team also includes essential non-academic partners providing financial resources and specialized tools for retinal surgery, macular transplantation, and stem cell engineering. The involvement of non-academic partners and end-users (retinal surgeons) in this project will help us reach the commercialization phase, which is the bottleneck of translational research. This project is thus highly competitive at the international level. |
01/01/2020 |
31/01/2022 |
| 2020 |
May Griffith (C) |
Université de Montréal |
Subventions de soutien aux partenariats biotechnologiques |
Bernier |
Cochercheur |
Gilbert Bernier, May Griffith, Jean-François Bouchard |
66 000 |
Photoreceptor transplantation for the treatment of retinal degenerative diseases |
Oculaire |
|
Retinal degenerative diseases including age-related macular degeneration is the leading cause of Canadian and global vision loss after cataracts; and there are no reliable treatments. Our project aimed at photoreceptor stem cell transplantation therapy is unique Canadian and is developed by our internationally renowned interdisciplinary team with expertise in stem cell and biomaterials engineering, vision function analysis and retinal transplantation surgery. The use of novel anti-angiogenic and pro-survival agents in photoreceptor cell transplantation therapy is of interest to academia, while the resulting intellectual property is of commercial significance. Current objectives for this grant are to implement a proof-of-principle of macular transplantation therapy in non-human primates, confirm safety of the cell transplantation therapy, and validate the use of a universal donor induced pluripotent cell line for generation of therapeutic cone photoreceptors. Deliverables include the demonstration of functional vision restoration in a non-human primate model of macular degeneration, and confirmation of the functionality and non-immunogenic nature of our universal donor cell line. We anticipate that successful completion of this proposed project will help restoring or improving central vision in patients suffering from late-stage RP, Stargardt’s disease, cone dystrophies, cone/rod dystrophies and age-related macular degeneration. The clinical, social and economic impacts of this treatment is thus possibly considerable for Canadians and patients abroad. The ownership of the technology by a Canadian entity is also economically beneficial for Canadians and Canada in general. Importantly, the treatment should be widely accessible following the use of a universal donor cell line, allowing treatment of all patients at a predicted low cost. Our team also includes essential non-academic partners providing financial resources and specialized tools for retinal surgery, macular transplantation, and stem cell engineering. The involvement of non-academic partners and end-users (retinal surgeons) in this project will help us reach the commercialization phase, which is the bottleneck of translational research. This project is thus highly competitive at the international level. |
01/01/2020 |
31/01/2022 |
| 2020 |
Gilbert Bernier (P) |
Hôpital Maisonneuve-Rosemont |
Subventions de soutien aux partenariats biotechnologiques |
Bernier |
Chercheur principal |
Gilbert Bernier, May Griffith, Jean-François Bouchard |
368 000 |
Photoreceptor transplantation for the treatment of retinal degenerative diseases |
Oculaire; diverses maladies |
|
Retinal degenerative diseases including age-related macular degeneration is the leading cause of Canadian and global vision loss after cataracts; and there are no reliable treatments. Our project aimed at photoreceptor stem cell transplantation therapy is unique Canadian and is developed by our internationally renowned interdisciplinary team with expertise in stem cell and biomaterials engineering, vision function analysis and retinal transplantation surgery. The use of novel anti-angiogenic and pro-survival agents in photoreceptor cell transplantation therapy is of interest to academia, while the resulting intellectual property is of commercial significance. Current objectives for this grant are to implement a proof-of-principle of macular transplantation therapy in non-human primates, confirm safety of the cell transplantation therapy, and validate the use of a universal donor induced pluripotent cell line for generation of therapeutic cone photoreceptors. Deliverables include the demonstration of functional vision restoration in a non-human primate model of macular degeneration, and confirmation of the functionality and non-immunogenic nature of our universal donor cell line. We anticipate that successful completion of this proposed project will help restoring or improving central vision in patients suffering from late-stage RP, Stargardt’s disease, cone dystrophies, cone/rod dystrophies and age-related macular degeneration. The clinical, social and economic impacts of this treatment is thus possibly considerable for Canadians and patients abroad. The ownership of the technology by a Canadian entity is also economically beneficial for Canadians and Canada in general. Importantly, the treatment should be widely accessible following the use of a universal donor cell line, allowing treatment of all patients at a predicted low cost. Our team also includes essential non-academic partners providing financial resources and specialized tools for retinal surgery, macular transplantation, and stem cell engineering. The involvement of non-academic partners and end-users (retinal surgeons) in this project will help us reach the commercialization phase, which is the bottleneck of translational research. This project is thus highly competitive at the international level. |
01/01/2020 |
31/01/2022 |
| 2020 |
Massimiliano Paganelli (P) |
CHU Sainte-Justine |
Subventions de soutien aux partenariats biotechnologiques |
Paganelli |
Chercheur principal |
Massimiliano Paganelli |
500 000 |
iPSC-derived encapsulated liver tissue to treat acute liver failure: pivotal confirmation in large animals |
Insuffisance hépatique |
|
Liver failure is the common outcome of most progressive liver diseases, affecting millions of people worldwide. Acute liver failure (ALF) is an extremely severe, progressive syndrome resulting from a sudden insult (like a drug, virus or toxin) to a previously healthy liver that affects thousands of people every year. Patients with ALF need to receive a liver transplant within days from the diagnosis, before their disease becomes irreversibly too severe. Over the last 3 years, with the support of the Stem Cell Network and other provincial and federal funding agencies, we developed an implantable product derived from human stem cells capable of treating ALF, avoiding transplantation. We already showed that what we call the Encapsulated Liver Tissue (ELT) is capable to perform mature liver function in a dish. We also showed that the ELT is safe and effective in treating ALF in rodents, without the risk of rejection or tumor formation. The ELT showed a significant competitive edge over similar products that are being developed worldwide. To promote the development and maturation of this technology and ease its translation to the patients, we created a spin-off company (Morphocell Technologies) and licensed our IP. We are already working with this Canadian regenerative medicine company and with the Centre for Commercialization of Regenerative Medicine (CCRM) to transform the ELT into a safe product for human use. With this project, we will collaborate with Morphocell, CCRM and other Canadian leading experts and stakeholders to confirm the safety and efficacy of the ELT in a large animal model of ALF. This will allow moving this promising treatment towards a first clinical trial in patients with ALF. This grant will support Canadian leadership in this field, help the growth of a promising Canadian biotechnology company (contributing to job creation) and foster the creation of unique scientific and technical expertise. If successful, this project will bring closer to the patients what has been widely recognized as a disruptive treatment for liver disease, which could save and improve the quality of life of thousands of patients with ALF and hundreds of thousands with chronic liver failure, worldwide. |
01/01/2020 |
31/01/2022 |
| 2020 |
Corrine Hoesli (C) |
Université McGill |
Subventions de soutien aux partenariats biotechnologiques |
Kieffer |
Cochercheur |
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli |
130 000 |
A Bioprinted Insulin-Producing Device for Diabetes |
Diabète |
|
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market. |
01/01/2020 |
31/01/2022 |
| 2020 |
Megan Levings (C) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Kieffer |
Cochercheur |
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli |
90 000 |
A Bioprinted Insulin-Producing Device for Diabetes |
Diabète |
|
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market. |
01/01/2020 |
31/01/2022 |
| 2020 |
Steven Paraskevas (C) |
Université McGill |
Subventions de soutien aux partenariats biotechnologiques |
Kieffer |
Cochercheur |
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli |
70 000 |
A Bioprinted Insulin-Producing Device for Diabetes |
Diabète |
|
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market. |
01/01/2020 |
31/01/2022 |
| 2020 |
James Piret (C) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Kieffer |
Cochercheur |
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli |
80 000 |
A Bioprinted Insulin-Producing Device for Diabetes |
Diabète |
|
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market. |
01/01/2020 |
31/01/2022 |
| 2020 |
Timothy Kieffer (P) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Kieffer |
Chercheur principal |
Timothy Kieffer, James Piret, Steven Paraskevas, Megan Levings, Corrine Hoesli |
130 000 |
A Bioprinted Insulin-Producing Device for Diabetes |
Diabète |
|
Injecting insulin has been extensively used to treat diabetes for almost a century. However, daily insulin injections do not adequately maintain blood sugar at normal levels, leading to damage throughout the body. While excellent blood sugar control without insulin injection can be achieved by transplantation of donor pancreas or insulin-producing islets, this strategy is severely limited by lack of available donors and requirement for life-long immune-suppression, thus hampering its broader application to treat diabetes. Aspect Biosystems has developed a proprietary bioprinting platform for manufacturing human tissues on demand to replace the need for donor organ transplants. This proposal aims to accelerate Aspect’s pre-clinical development of a therapeutic pancreatic tissue patch as a therapy for type 1 diabetes that does not rely on daily insulin injections or cadaveric donor islets. This objective will be accomplished by bringing together Canadian expertise in islet transplant biology led by academic PI, Dr. Timothy Kieffer and an existing collaborative network. The team will work together to tackle three key challenge areas for islet transplantation programs by: 1) providing a sustainable stem cell-derived source of insulin-producing beta cells that can be manufactured to scale for therapeutic efficacy and has already been shown to restore euglycemia in gold-standard animal models of diabetes in Dr. Kieffer’s lab; 2) offering device manufacturing and material processing solutions for optimization of pancreatic tissue patch design that maximally supports beta-cell fitness and function in a manner that maintains immune-protection through bioengineering capabilities and analytical tools in the laboratories of Drs. Corinne Hoesli and James Piret; and 3) access to surgical transplantation expertise in order to confidently demonstrate pre-clinical efficacy of an immune-protected pancreatic tissue patch using human relevant immune cell tools developed by Dr. Megan Levings in addition to human islet transplantation clinical insight from Dr. Steven Paraskevas as an anticipated therapeutic tissue patch device adopter. The project will provide direct benefits to Canada through improved health for patients with diabetes and reduced burden of health care cost, while also creating commercial opportunities and a future revenue stream for a Canadian based biotechnology company aiming to enter the regenerative medicine market. |
01/01/2020 |
31/01/2022 |
| 2020 |
Dean Fergusson (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien aux partenariats biotechnologiques |
Thébaud |
Cochercheur |
Bernard Thébaud, Sarah Wooton, Dean Fergusson |
5 000 |
AAVenger: Adeno-Associated Virus Engineered Gene Epithelial progenitor cell Regeneration |
Poumon, poumons, thérapie génique, thérapies géniques |
|
Air sacs deep in the lung called alveoli are coated with surfactant. Surfactant keeps alveoli open to ensure efficient exchange of oxygen and waste carbon dioxide. Surfactant is produced by progenitor cells in the deep lung (type 2 alveolar epithelial cells, AT2). Surfactant proteins (such as SP-B, SP-C) or surfactant-associated ABCA3 are critical for normal lung function. Mutations in these surfactant protein genes cause severe failure to breathe at birth and are invariably lethal. More of these genetic lung diseases that declare themselves later in life in children and young adults are increasingly recognized and result in debilitating interstitial lung diseases (lung scarring) due to destruction of AT2 cells. The only treatment option is lung transplantation, which is not always feasible. Novel therapies for surfactant deficiencies are urgently needed.
We have engineered a novel regenerative medicine platform based on a gene therapy to cure these untreatable lung diseases. SP-B deficiency is Inspire Biotherapeutics’ lead indication. Our platform utilizes an engineered AAV capsid, with unprecedented efficiency in targeting the necessary AT2 lung stem/progenitor cells to deliver a normal copy of the SP-B gene and enable disease correction. Airway delivery of AAV-SP-B in deficient mice restores SP-B expression, improves lung injury and function and dramatically enhances survival to up to 6 months compared to 3-4 days in untreated controls.
Here, we propose to overcome the main obstacles to bringing a regenerative gene therapy into patients: establish the efficient large-scale manufacturing of AAV and demonstrate vector safety and tolerability in toxicology studies. The scalable AAV manufacturing process will enable the expansion of our AAVenger platform, utilizing our patented gene therapy technology and novel molecular and genetic tools, to produce clinical trial-ready gene therapies for a wide range of life-threatening and debilitating lung diseases affecting Canadians and patients world-wide. Our multi-disciplinary team has successfully collaborated over the past three years and highlights Canadian excellence and leadership in regenerative medicine, gene therapy, manufacturing and clinical trials. This grant will support the acceleration of a promising Canadian Regenerative Medicine biotechnology company, grow unique scientific and technical expertise, and create jobs for a new breed of HQP. |
01/09/2020 |
28/02/2022 |
| 2020 |
Sarah Wooton (C) |
University of Guelph |
Subventions de soutien aux partenariats biotechnologiques |
Thébaud |
Cochercheur |
Bernard Thébaud, Sarah Wooton, Dean Fergusson |
35 000 |
AAVenger: Adeno-Associated Virus Engineered Gene Epithelial progenitor cell Regeneration |
Poumon, poumons, thérapie génique, thérapies géniques |
|
Air sacs deep in the lung called alveoli are coated with surfactant. Surfactant keeps alveoli open to ensure efficient exchange of oxygen and waste carbon dioxide. Surfactant is produced by progenitor cells in the deep lung (type 2 alveolar epithelial cells, AT2). Surfactant proteins (such as SP-B, SP-C) or surfactant-associated ABCA3 are critical for normal lung function. Mutations in these surfactant protein genes cause severe failure to breathe at birth and are invariably lethal. More of these genetic lung diseases that declare themselves later in life in children and young adults are increasingly recognized and result in debilitating interstitial lung diseases (lung scarring) due to destruction of AT2 cells. The only treatment option is lung transplantation, which is not always feasible. Novel therapies for surfactant deficiencies are urgently needed.
We have engineered a novel regenerative medicine platform based on a gene therapy to cure these untreatable lung diseases. SP-B deficiency is Inspire Biotherapeutics’ lead indication. Our platform utilizes an engineered AAV capsid, with unprecedented efficiency in targeting the necessary AT2 lung stem/progenitor cells to deliver a normal copy of the SP-B gene and enable disease correction. Airway delivery of AAV-SP-B in deficient mice restores SP-B expression, improves lung injury and function and dramatically enhances survival to up to 6 months compared to 3-4 days in untreated controls.
Here, we propose to overcome the main obstacles to bringing a regenerative gene therapy into patients: establish the efficient large-scale manufacturing of AAV and demonstrate vector safety and tolerability in toxicology studies. The scalable AAV manufacturing process will enable the expansion of our AAVenger platform, utilizing our patented gene therapy technology and novel molecular and genetic tools, to produce clinical trial-ready gene therapies for a wide range of life-threatening and debilitating lung diseases affecting Canadians and patients world-wide. Our multi-disciplinary team has successfully collaborated over the past three years and highlights Canadian excellence and leadership in regenerative medicine, gene therapy, manufacturing and clinical trials. This grant will support the acceleration of a promising Canadian Regenerative Medicine biotechnology company, grow unique scientific and technical expertise, and create jobs for a new breed of HQP. |
01/09/2020 |
28/02/2022 |
| 2020 |
Bernard Thébaud (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien aux partenariats biotechnologiques |
Thébaud |
Chercheur principal |
Bernard Thébaud, Sarah Wooton, Dean Fergusson |
324 000 |
AAVenger: Adeno-Associated Virus Engineered Gene Epithelial progenitor cell Regeneration |
Poumon, poumons, thérapie génique, thérapies géniques |
|
Air sacs deep in the lung called alveoli are coated with surfactant. Surfactant keeps alveoli open to ensure efficient exchange of oxygen and waste carbon dioxide. Surfactant is produced by progenitor cells in the deep lung (type 2 alveolar epithelial cells, AT2). Surfactant proteins (such as SP-B, SP-C) or surfactant-associated ABCA3 are critical for normal lung function. Mutations in these surfactant protein genes cause severe failure to breathe at birth and are invariably lethal. More of these genetic lung diseases that declare themselves later in life in children and young adults are increasingly recognized and result in debilitating interstitial lung diseases (lung scarring) due to destruction of AT2 cells. The only treatment option is lung transplantation, which is not always feasible. Novel therapies for surfactant deficiencies are urgently needed.
We have engineered a novel regenerative medicine platform based on a gene therapy to cure these untreatable lung diseases. SP-B deficiency is Inspire Biotherapeutics’ lead indication. Our platform utilizes an engineered AAV capsid, with unprecedented efficiency in targeting the necessary AT2 lung stem/progenitor cells to deliver a normal copy of the SP-B gene and enable disease correction. Airway delivery of AAV-SP-B in deficient mice restores SP-B expression, improves lung injury and function and dramatically enhances survival to up to 6 months compared to 3-4 days in untreated controls.
Here, we propose to overcome the main obstacles to bringing a regenerative gene therapy into patients: establish the efficient large-scale manufacturing of AAV and demonstrate vector safety and tolerability in toxicology studies. The scalable AAV manufacturing process will enable the expansion of our AAVenger platform, utilizing our patented gene therapy technology and novel molecular and genetic tools, to produce clinical trial-ready gene therapies for a wide range of life-threatening and debilitating lung diseases affecting Canadians and patients world-wide. Our multi-disciplinary team has successfully collaborated over the past three years and highlights Canadian excellence and leadership in regenerative medicine, gene therapy, manufacturing and clinical trials. This grant will support the acceleration of a promising Canadian Regenerative Medicine biotechnology company, grow unique scientific and technical expertise, and create jobs for a new breed of HQP. |
01/09/2020 |
28/02/2022 |
| 2020 |
Peter Zandstra (P) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Zandstra |
Chercheur principal |
Peter Zandstra, David Knapp, Robert Holt |
266 300 |
Enabling a platform for customized pluripotent stem cell derived T-cell therapies |
Sang, CAR-T |
|
Underlying the genesis and progression of many chronic illnesses including cancer, diabetes, heart disease, auto-immunity, and immunodeficiency, is dysfunction of immune cells. T-lymphocyte cells develop within the thymus, and are part of the adaptive immune system which includes cytotoxic T-cells that mediate defence against cancer cells and intracellular pathogens, including viruses. Cellular therapies with genetically engineered cytotoxic T-cells, e.g. CAR or TCR T-cells, designed to attack cancer cells, have shown tremendous efficacy as anti-cancer therapies. However, as mature T-cells from patients are used in this process, successful implementation of this strategy is limited by high treatment costs, low cell yields, and compromised function of the thymus in some patients. Consequently, a robust and renewable supply of normal and engineered T-cells would transform clinical applications.
Our research team is led by Dr. Peter Zandstra, a world leader and innovator in stem cell-based, Dr. Robert Holt, an expert in T-cell receptor engineering and leading lead in a pan-Canadian effort to conduct the first Phase I/II anti-CD19 CAR T-cell therapy trial in Canada using Canadian-made vectors and cells, and Dr. David Knapp, an emerging leader with expertise in applying cutting-edge genomic approaches to advance the study of blood cell differentiation. Dr. Zandstra and collaborator Dr. Juan Carlos Zúñiga-Pflücker previously established a clinically relevant in vitro engineered thymic niche system to generate progenitor T-cells from human blood stem cells. The combination of this technology with genetically modified human pluripotent stem cells (hPSC) could profoundly transform therapeutic applications of immune system related diseases.
To make T-cell therapies, including CAR T-cells, more scalable, cost-effective, and rapidly available to Canadians, our research team will work with Notch Therapeutics Inc., founded by Drs. Zandstra and Zúñiga-Pflücker, on developing a platform, called the Engineered Thymic Niche (ETN), to differentiate T-cells from human pluripotent stem cells (hPSCs), an unlimited cell source. We will use this platform to develop proof of concept T-cell therapeutics including engineered cytotoxic T-cells targeting Epstein Barr Virus (EBV) infected cells, that will lay the foundation for clinical trials to treat cancer and other diseases, and will enable multiple cell therapeutic applications. |
01/09/2020 |
28/02/2022 |
| 2020 |
David Knapp (C) |
Université de Montréal |
Subventions de soutien aux partenariats biotechnologiques |
Zandstra |
Cochercheur |
Peter Zandstra, David Knapp, Robert Holt |
40 000 |
Enabling a platform for customized pluripotent stem cell derived T-cell therapies |
Sang, CAR-T |
|
Underlying the genesis and progression of many chronic illnesses including cancer, diabetes, heart disease, auto-immunity, and immunodeficiency, is dysfunction of immune cells. T-lymphocyte cells develop within the thymus, and are part of the adaptive immune system which includes cytotoxic T-cells that mediate defence against cancer cells and intracellular pathogens, including viruses. Cellular therapies with genetically engineered cytotoxic T-cells, e.g. CAR or TCR T-cells, designed to attack cancer cells, have shown tremendous efficacy as anti-cancer therapies. However, as mature T-cells from patients are used in this process, successful implementation of this strategy is limited by high treatment costs, low cell yields, and compromised function of the thymus in some patients. Consequently, a robust and renewable supply of normal and engineered T-cells would transform clinical applications.
Our research team is led by Dr. Peter Zandstra, a world leader and innovator in stem cell-based, Dr. Robert Holt, an expert in T-cell receptor engineering and leading lead in a pan-Canadian effort to conduct the first Phase I/II anti-CD19 CAR T-cell therapy trial in Canada using Canadian-made vectors and cells, and Dr. David Knapp, an emerging leader with expertise in applying cutting-edge genomic approaches to advance the study of blood cell differentiation. Dr. Zandstra and collaborator Dr. Juan Carlos Zúñiga-Pflücker previously established a clinically relevant in vitro engineered thymic niche system to generate progenitor T-cells from human blood stem cells. The combination of this technology with genetically modified human pluripotent stem cells (hPSC) could profoundly transform therapeutic applications of immune system related diseases.
To make T-cell therapies, including CAR T-cells, more scalable, cost-effective, and rapidly available to Canadians, our research team will work with Notch Therapeutics Inc., founded by Drs. Zandstra and Zúñiga-Pflücker, on developing a platform, called the Engineered Thymic Niche (ETN), to differentiate T-cells from human pluripotent stem cells (hPSCs), an unlimited cell source. We will use this platform to develop proof of concept T-cell therapeutics including engineered cytotoxic T-cells targeting Epstein Barr Virus (EBV) infected cells, that will lay the foundation for clinical trials to treat cancer and other diseases, and will enable multiple cell therapeutic applications. |
01/09/2020 |
28/02/2022 |
| 2020 |
Robert Holt (C) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Zandstra |
Cochercheur |
Peter Zandstra, David Knapp, Robert Holt |
43 700 |
Enabling a platform for customized pluripotent stem cell derived T-cell therapies |
Sang, CAR-T |
|
Underlying the genesis and progression of many chronic illnesses including cancer, diabetes, heart disease, auto-immunity, and immunodeficiency, is dysfunction of immune cells. T-lymphocyte cells develop within the thymus, and are part of the adaptive immune system which includes cytotoxic T-cells that mediate defence against cancer cells and intracellular pathogens, including viruses. Cellular therapies with genetically engineered cytotoxic T-cells, e.g. CAR or TCR T-cells, designed to attack cancer cells, have shown tremendous efficacy as anti-cancer therapies. However, as mature T-cells from patients are used in this process, successful implementation of this strategy is limited by high treatment costs, low cell yields, and compromised function of the thymus in some patients. Consequently, a robust and renewable supply of normal and engineered T-cells would transform clinical applications.
Our research team is led by Dr. Peter Zandstra, a world leader and innovator in stem cell-based, Dr. Robert Holt, an expert in T-cell receptor engineering and leading lead in a pan-Canadian effort to conduct the first Phase I/II anti-CD19 CAR T-cell therapy trial in Canada using Canadian-made vectors and cells, and Dr. David Knapp, an emerging leader with expertise in applying cutting-edge genomic approaches to advance the study of blood cell differentiation. Dr. Zandstra and collaborator Dr. Juan Carlos Zúñiga-Pflücker previously established a clinically relevant in vitro engineered thymic niche system to generate progenitor T-cells from human blood stem cells. The combination of this technology with genetically modified human pluripotent stem cells (hPSC) could profoundly transform therapeutic applications of immune system related diseases.
To make T-cell therapies, including CAR T-cells, more scalable, cost-effective, and rapidly available to Canadians, our research team will work with Notch Therapeutics Inc., founded by Drs. Zandstra and Zúñiga-Pflücker, on developing a platform, called the Engineered Thymic Niche (ETN), to differentiate T-cells from human pluripotent stem cells (hPSCs), an unlimited cell source. We will use this platform to develop proof of concept T-cell therapeutics including engineered cytotoxic T-cells targeting Epstein Barr Virus (EBV) infected cells, that will lay the foundation for clinical trials to treat cancer and other diseases, and will enable multiple cell therapeutic applications. |
01/09/2020 |
28/02/2022 |
| 2020 |
Bartha Knoppers (P) |
Université McGill |
Application et société |
Knoppers |
Chercheur principal |
Bartha Knoppers |
74 836 |
Ethical and Legal Framework for Direct-to-Participant (DTP) Recruitment |
QEJS, questions éthiques, juridiques et sociales; recrutement des patients |
|
An important impediment to research progress in stem cell research, particularly for rare diseases, is the recruitment of participants for data and sample collection. Addressing this challenge, Canadian researchers are currently exploring the use of international Direct-to-Participant (DTP) recruitment, a novel recruitment strategy harnessing the communication and networking potential of the internet and social media platforms. DTP will impact how research studies are conducted as the model allows the direct recruitment, consenting and enrollment of participants via the internet without involvement from other researchers or institutions/hospitals. Presently, the benefits of DTP recruitment are unknown while little research has been conducted regarding the ethical/legal implications of this methodology. Likewise, there is a lack of national and international guidance for the appropriate and legitimate uses of DTP recruitment, as well as how best to resolve the ethical/legal concerns that can unfold, since many countries – including Canada – have yet to clearly address the issue. The absence of proper governance presents challenges for researchers when navigating the different regulatory and ethical requirements and increases the likelihood of risks to participants.
The main objective of this project is to fill this ethical and policy gap by: i) examining the ethical/legal issues of international DTP recruitment (for adult and minor participants), and ii) yielding concrete, practical ethical guidance and tools for Canadian researchers and REBs. In collaboration with the Program for Individualized Cystic Fibrosis Therapy (CFIT) at SickKids, we will first build a case study to examine the feasibility and utility of international DTP recruitment, while producing practical, context specific governance framework and recruitment tools. Knowledge and pragmatic experience gained from the CFIT case study, along with consultations with national stakeholders (REB representatives, researchers, oversight agencies and policy makers), will contribute to the development of Canadian Best Practice Guidelines for DTP recruitment. As innovative and fundamental resources for Canadian REBs and researchers, the guidelines and practical tools will directly address an immediate need for clear policy and guidance for international DTP recruitment in stem cell research. They will also set the standards for Canada and internationally, consolidating Canada’s position as a leader in policy development. |
01/01/2020 |
31/01/2022 |
| 2020 |
Kelly Cobey (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions du programme Applications et Société |
Thébaud |
Cochercheur |
Bernard Thébaud, Manoj Lalu, Kelly Cobey |
15 000 |
Clearing-up the stem-cell-mess: Delphi-based definition and reporting guidelines to improve transparency in MSC research |
QEJS, questions éthiques, juridiques et sociales, CSM |
|
Mesenchymal Stromal Cells (MSCs) have been tested in more than 1000 clinical trials. Despite promising results in different laboratory models, MSC clinical trials demonstrate inconsistent results regarding their clinical efficacy. One explanation is that there is a wide variation in the quality of the descriptions of what they define as an MSC, how they produced MSCs, and which patients they treated. As a consequence, the results of these studies are difficult to reproduce, compare and generalize. Therefore, it is critical that our research community develops a clear definition of what MSCs are, as well as guidelines on how to properly report MSC clinical trials.
To address these concerns, we will recruit international experts on MSCs to participate in a consensus generating process called the Delphi method. Our Delphi consists of three rounds of consensus building questions answered electronically. In the first three rounds, a Core Group, along with a broader group of MSC researchers, answer specific questions via an online survey about how to define MSCs and what items should be mandatory to properly report results of an MSC clinical study. A additional fourth round occurs in person and will be attended by the Core Group. Between Delphi rounds the questionnaire is modified according to the experts’ responses. Feedback from the group's responses (e.g. aggregate ratings of items, comments) are provided to each respondent after each round to build consensus. Inclusion or exclusion of an item will be defined by 80% agreement in responses among the group.
Providing a universally accepted definition of MSCs and guidelines on how to report clinical trials using MSCs will improve the quality, transparency and reproducibility of MSC research. To ensure uptake of our guidelines, we will develop tools and resources to increase awareness and to implement our consensus definition and reporting guidelines. This will include a dedicated website of resources that hosts freely available educational content, FAQ sheets, infographics, examples of how to successfully apply the definition and reporting guideline, and a list of stakeholders who have endorsed and implemented our recommendations.
“To maximize the benefit to society, you need not to just do research but do it well”, Doug Altman. |
01/09/2020 |
28/02/2022 |
| 2020 |
Manoj Lalu (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions du programme Applications et Société |
Thébaud |
Cochercheur |
Bernard Thébaud, Manoj Lalu, Kelly Cobey |
58 500 |
Clearing-up the stem-cell-mess: Delphi-based definition and reporting guidelines to improve transparency in MSC research |
QEJS, questions éthiques, juridiques et sociales, CSM |
|
Mesenchymal Stromal Cells (MSCs) have been tested in more than 1000 clinical trials. Despite promising results in different laboratory models, MSC clinical trials demonstrate inconsistent results regarding their clinical efficacy. One explanation is that there is a wide variation in the quality of the descriptions of what they define as an MSC, how they produced MSCs, and which patients they treated. As a consequence, the results of these studies are difficult to reproduce, compare and generalize. Therefore, it is critical that our research community develops a clear definition of what MSCs are, as well as guidelines on how to properly report MSC clinical trials.
To address these concerns, we will recruit international experts on MSCs to participate in a consensus generating process called the Delphi method. Our Delphi consists of three rounds of consensus building questions answered electronically. In the first three rounds, a Core Group, along with a broader group of MSC researchers, answer specific questions via an online survey about how to define MSCs and what items should be mandatory to properly report results of an MSC clinical study. A additional fourth round occurs in person and will be attended by the Core Group. Between Delphi rounds the questionnaire is modified according to the experts’ responses. Feedback from the group's responses (e.g. aggregate ratings of items, comments) are provided to each respondent after each round to build consensus. Inclusion or exclusion of an item will be defined by 80% agreement in responses among the group.
Providing a universally accepted definition of MSCs and guidelines on how to report clinical trials using MSCs will improve the quality, transparency and reproducibility of MSC research. To ensure uptake of our guidelines, we will develop tools and resources to increase awareness and to implement our consensus definition and reporting guidelines. This will include a dedicated website of resources that hosts freely available educational content, FAQ sheets, infographics, examples of how to successfully apply the definition and reporting guideline, and a list of stakeholders who have endorsed and implemented our recommendations.
“To maximize the benefit to society, you need not to just do research but do it well”, Doug Altman. |
01/09/2020 |
28/02/2022 |
| 2020 |
Bernard Thébaud (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions du programme Applications et Société |
Thébaud |
Chercheur principal |
Bernard Thébaud, Manoj Lalu, Kelly Cobey |
101 500 |
Clearing-up the stem-cell-mess: Delphi-based definition and reporting guidelines to improve transparency in MSC research |
QEJS, questions éthiques, juridiques et sociales, CSM |
|
Mesenchymal Stromal Cells (MSCs) have been tested in more than 1000 clinical trials. Despite promising results in different laboratory models, MSC clinical trials demonstrate inconsistent results regarding their clinical efficacy. One explanation is that there is a wide variation in the quality of the descriptions of what they define as an MSC, how they produced MSCs, and which patients they treated. As a consequence, the results of these studies are difficult to reproduce, compare and generalize. Therefore, it is critical that our research community develops a clear definition of what MSCs are, as well as guidelines on how to properly report MSC clinical trials.
To address these concerns, we will recruit international experts on MSCs to participate in a consensus generating process called the Delphi method. Our Delphi consists of three rounds of consensus building questions answered electronically. In the first three rounds, a Core Group, along with a broader group of MSC researchers, answer specific questions via an online survey about how to define MSCs and what items should be mandatory to properly report results of an MSC clinical study. A additional fourth round occurs in person and will be attended by the Core Group. Between Delphi rounds the questionnaire is modified according to the experts’ responses. Feedback from the group's responses (e.g. aggregate ratings of items, comments) are provided to each respondent after each round to build consensus. Inclusion or exclusion of an item will be defined by 80% agreement in responses among the group.
Providing a universally accepted definition of MSCs and guidelines on how to report clinical trials using MSCs will improve the quality, transparency and reproducibility of MSC research. To ensure uptake of our guidelines, we will develop tools and resources to increase awareness and to implement our consensus definition and reporting guidelines. This will include a dedicated website of resources that hosts freely available educational content, FAQ sheets, infographics, examples of how to successfully apply the definition and reporting guideline, and a list of stakeholders who have endorsed and implemented our recommendations.
“To maximize the benefit to society, you need not to just do research but do it well”, Doug Altman. |
01/09/2020 |
28/02/2022 |
| 2022 |
Véronique Moulin (P) |
Université Laval |
Subventions de soutien des essais cliniques |
Moulin |
Chercheur principal |
Véronique Moulin |
581 700 |
Tissue engineering to treat Canadian burn patients: the Self-Assembled Skin Substitutes (SASS) |
Brûlures, brûlure |
tissue engineering, skin, burn, acute wound, repair, clinical trial, stem cells |
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites. With the tissue engineering methods developed in our lab, autologous Self-Assembled Skin Substitutes (SASS) can be produced and could permanently cover all the patient wounds. This early phase clinical trial has now been accepted by Health Canada and 14 patients have been treated. The objective is to complete the clinical trial and apply for Health Canada authorization to offer our product in Canada.
To reach this goal, we will collaborate with surgeons that are dedicated to treating burn patients. We speculate that SASS treatment will have economic and social benefits as our preliminary results demonstrated that treatment decreases morbidity caused by standard treatments and improves the quality of the post-burn scars.
Our team is composed of four internationally known researchers in regenerative medicine from two universities and of plastic surgeons working in major Canadian burn unit sites. Manufacturing SASS in a tissue processing centre built and directed by our team, we are the only Canadian team dedicated to the reconstruction of organized tissues to treat patients. Following acceptance by Health Canada, we will be the first team in Canada to routinely treat patients with autologous reconstructed skin. |
01/01/1970 |
01/01/1970 |
| 2022 |
David Thompson (P) |
University of British Columbia |
Subventions de soutien des essais cliniques |
Thompson |
Chercheur principal |
David Thompson |
1 000 000 |
Clinical Trial of the First Gene-Edited Cell Replacement Therapy for Type 1 Diabetes |
Diabète |
Diabetes, stem cells, pancreatic islet, implant, macroencapsulation, immune-evasive, gene editing |
Diabetes is a debilitating disorder of high blood sugar that afflicts millions of Canadians. People living with type 1 diabetes lack the cells that release the hormone insulin, so multiple daily insulin injections remain the conventional way to control blood sugar levels and survive. We and others have demonstrated that transplant of clusters of insulin-producing cells, called islets, can reduce or even eliminate insulin injections. Unfortunately, the only source of islets for transplant is recently deceased donors and only a tiny fraction of those in need can receive them. There have been remarkable breakthroughs in unraveling the process by which islet cells develop naturally in the body. As a result, it is now possible to replicate this process in the lab with cultured stem cells. We have been conducting clinical trials in which islet precursor cells generated from stem cells are loaded into thin devices and implanted under the skin. Our initial assessments are very encouraging, but patients are required to take powerful immunosuppressants. Now in a world’s first we will test cells that have been genetically engineered to be stealthy such that we can achieve our objective of transplanting the cells without the need for immunosuppression. If successful, this innovative approach could provide a cure for diabetes, freeing Canadians from insulin injections, debilitating complications, and the economic burden of this disease. |
01/01/1970 |
01/01/1970 |
| 2022 |
Lauralyn McIntyre (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien des essais cliniques |
McIntyre |
Chercheur principal |
Lauralyn McIntyre |
999 850 |
Umbilical Mesenchymal Stem Cells as Cellular Immunotherapy for Septic Shock (UC-CISS): A Phase II RCT |
Septicémie; choc septique |
Mesenchymal Stromal Cells, Sepsis, Septic Shock, Randomized Controlled Trial, Allogeneic, Cryopreserved, Stem Cell |
Severe infection with shock (septic shock) in the intensive care unit (ICU) accounts for approximately 20% of admissions, of which 20 to 40% will die. Septic shock is associated with an uncontrolled inflammatory response that is initiated by an infectious organism. Studies done in septic animals suggest that the infusion of mesenchymal stem cells (MSCs) balance inflammation, help with repair of injured organs, and reduce death. Hence, it represents a promising potential therapy for septic shock._x000D_
We completed the first in the World Phase I safety trial of MSCs (n=9) versus controls (n=21) in 30 patients with septic shock (CISS Phase I trial). The CISS Phase I trial results confirmed the optimum dose and that treatment with MSCs is safe._x000D_
The Phase II trial (UC-CISS II) will determine whether MSCs as compared to placebo reduce organ failures. UC-CISS II will also continue to evaluate safety and determine whether MSCs improve clinical and patient important outcomes. UC-CISS II will randomize 122 ICU patients with septic shock to previously frozen MSCs or placebo across Canadian centers. The frequency of adverse events (AEs) and serious AEs will be recorded. Blood will be drawn for inflammation markers and the effectiveness of MSC therapy as compared to its cost will be evaluated. _x000D_
UC-CISS II results will be used to support an international Phase III MSC trial which if positive could save thousands of lives and restore the function and quality of life of septic shock survivors. |
01/01/1970 |
01/01/1970 |
| 2022 |
Anastasia Tikhonova (P) |
University Health Network |
Subventions de démarrage pour chercheurs en début de carrière |
Tikhonova |
Chercheur principal |
Anastasia Tikhonova, Courtney Jones |
255 750 |
Targeting the bone marrow microenvironment to promote hematopoietic regeneration |
Cancer |
Bone marrow niche, hematopoiesis, hematopoietic regeneration, bone marrow microenvironment, hematopoietic stem cell transplantation, metabolism |
Patients with cancers are often treated with multiple rounds of chemotherapy. Many patients receiving chemotherapy also develop long-term bone injury and have compromised blood cell development. Blood stem cells are maintained by specialized “support cells” in the bone marrow. Dysfunction of bone marrow support cells has been linked to bone marrow transplant failure. However, what causes this dysfunction and whether it can be reversed to improve transplantation is not known. Using state-of-the-art techniques, we will study the impact of different chemotherapy agents on blood stem cells and their surrounding ecosystem. Our ultimate goal is to define the optimal bone marrow conditions, to improve the quality of life of cancer survivors. |
01/01/1970 |
01/01/1970 |
| 2022 |
Courtney Jones (C) |
University Health Network |
Subventions de démarrage pour chercheurs en début de carrière |
Tikhonova |
Cochercheur |
Anastasia Tikhonova, Courtney Jones |
44 250 |
Targeting the bone marrow microenvironment to promote hematopoietic regeneration |
Cancer |
Bone marrow niche, hematopoiesis, hematopoietic regeneration, bone marrow microenvironment, hematopoietic stem cell transplantation, metabolism |
Patients with cancers are often treated with multiple rounds of chemotherapy. Many patients receiving chemotherapy also develop long-term bone injury and have compromised blood cell development. Blood stem cells are maintained by specialized “support cells” in the bone marrow. Dysfunction of bone marrow support cells has been linked to bone marrow transplant failure. However, what causes this dysfunction and whether it can be reversed to improve transplantation is not known. Using state-of-the-art techniques, we will study the impact of different chemotherapy agents on blood stem cells and their surrounding ecosystem. Our ultimate goal is to define the optimal bone marrow conditions, to improve the quality of life of cancer survivors. |
01/01/1970 |
01/01/1970 |
| 2022 |
Mamatha Bhat (P) |
University Health Network |
Subventions de démarrage pour chercheurs en début de carrière |
Bhat |
Chercheur principal |
Mamatha Bhat |
300 000 |
A Nanoparticle-based Strategy to Therapeutically Restore Regenerative Capacity in Cirrhotic Livers |
Maladies du foie, maladie du foie, maladie hépatique |
Liver Regeneration, Sex, Fibrosis, NASH Cirrhosis, Network Analysis, Single Cell Profiling, Nanoparticles |
The liver is the only internal organ in the body that can quickly regenerate. One in four Canadians is affected by liver disease. Liver disease is often silent and scars the liver, causing cirrhosis over many years, which reduces its ability to regenerate. Almost a third of these people will die or become ineligible for a liver transplant. To help patients with end-stage liver disease, we need to understand what makes the liver regenerate and harness this as a therapeutic strategy. _x000D_
_x000D_
We know that one of the signaling pathways, called the Hippo-YAP, controls tissue regeneration. When we remove part of the liver in mice, rapid liver regeneration increases the number of YAP-dependent genes, which are reduced in presence of fibrosis. However, fibrotic livers that regenerate are able to rescue the liver from worsening scarring. To better understand the mechanisms driving liver regeneration despite scarring, we will use single-cell profiling technology to identify genes in livers that retain the capacity to regenerate. We will then examine a liver-selective lipid-based particles strategy to see if it can help improve regeneration even when the liver is scarred, while sparing the rest of body any side effects. _x000D_
_x000D_
This project will provide the first steps towards a unique therapeutic strategy to rescue defective liver regeneration in patients with chronic liver disease and help them live longer._x000D_
_x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Sheila Teves (P) |
University of British Columbia |
Subventions de démarrage pour chercheurs en début de carrière |
Teves |
Chercheur principal |
Sheila Teves |
300 000 |
Transcription regulation of hiPSC-derived cardiomyocytes during maturation and hypertrophic cardiomyopathy |
Cardiaque; cardiomyopathie hypertrophique |
Transcription factor, gene regulation, chromatin, mTOR signaling, human induced pluriptent stem cells, hypertrophic cardiomyopathy |
Heart disease is the leading cause of death worldwide, with almost 9 million deaths globally in 2019 alone. In the US, 1 in every 4 deaths is due to heart failure, with estimated costs to the US economy at about $219 billion each year. More importantly, as the population on average is living longer, heart disease is on the rise. Therefore, demand for better interventions and treatments will increase over time._x000D_
One challenge with developing new therapeutics for heart disease is that most of the research uses animal models that do not necessarily mimic human disease. Over the last two decades, scientists have discovered a way to convert adult human cells into a more stem cell-like state. These so-called induced pluripotent stem cells can then be differentiated into heart cells like cardiomyocytes. These patient derived cells provide a promising new system for heart disease drug screening, except that they fail to fully mature and instead resemble the immature cells seen in the inherited heart disease called hypertrophic cardiomyopathy. Therefore, the main goal of this proposed project is to discover the determining factors that allow for cardiomyocytes from human induced pluripotent stem cells to fully mature. We will use gene editing, genomics, and proteomics to learn how gene expression changes between immature and mature cardiomyocytes, and apply this knowledge towards identifying new targets for therapeutic intervention, specifically for hypertrophic cardiomyopathy. _x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Amy Wong (P) |
Hospital for Sick Children |
Subventions de démarrage pour chercheurs en début de carrière |
Wong |
Chercheur principal |
Amy Wong, Bo Wang, Nika Shakiba |
135 272 |
Deciphering cell competition during iPSC differentiation towards lung epithelia |
Fibrose kystique |
Single cell tracing, barcoding, epithelial cells, iPSC, differentiation, cell competition, computational modeling, artificial intelligence |
Lung disease is the third leading cause of death worldwide with very limited treatment options for end-stage lung diseases. Generating specific cells for cell-based airway regeneration to treat degenerative airway diseases such as cystic fibrosis is a promising approach. The lung is a highly complex organ comprised of >60 cell types that collectively play a vital role in breathing, gas exchange, acid-base balance, metabolism, and immunity. To generate specific cell types for tissue regeneration therefore remains a challenge especially since the mechanisms driving lung cell development is poorly understood. Advanced single cell technologies have provided further evidence that the adult lung is much more complex and new cell types and cell states have been identified both homeostatic and diseased conditions that can change the outcome of lung functions and repair. Understanding how these cells emerge can improve targeted cell derivation processes for airway cell replacement therapies. Here, we will leverage our ability to generate airway epithelial cell types from human pluripotent stem cells (hPSC) in culture to determine how specific cells emerge and the genetic factors (fitness genes) that enable certain cells to emerge and dominate over others. Our work will identify novel gene targets to selectively enhance cell fitness and enrich for specific cell types for targeted cell-based therapies to treat airway diseases. |
01/01/1970 |
01/01/1970 |
| 2022 |
Bo Wang (C) |
University Health Network |
Subventions de démarrage pour chercheurs en début de carrière |
Wong |
Cochercheur |
Amy Wong, Bo Wang, Nika Shakiba |
44 625 |
Deciphering cell competition during iPSC differentiation towards lung epithelia |
Fibrose kystique |
Single cell tracing, barcoding, epithelial cells, iPSC, differentiation, cell competition, computational modeling, artificial intelligence |
Lung disease is the third leading cause of death worldwide with very limited treatment options for end-stage lung diseases. Generating specific cells for cell-based airway regeneration to treat degenerative airway diseases such as cystic fibrosis is a promising approach. The lung is a highly complex organ comprised of >60 cell types that collectively play a vital role in breathing, gas exchange, acid-base balance, metabolism, and immunity. To generate specific cell types for tissue regeneration therefore remains a challenge especially since the mechanisms driving lung cell development is poorly understood. Advanced single cell technologies have provided further evidence that the adult lung is much more complex and new cell types and cell states have been identified both homeostatic and diseased conditions that can change the outcome of lung functions and repair. Understanding how these cells emerge can improve targeted cell derivation processes for airway cell replacement therapies. Here, we will leverage our ability to generate airway epithelial cell types from human pluripotent stem cells (hPSC) in culture to determine how specific cells emerge and the genetic factors (fitness genes) that enable certain cells to emerge and dominate over others. Our work will identify novel gene targets to selectively enhance cell fitness and enrich for specific cell types for targeted cell-based therapies to treat airway diseases. |
01/01/1970 |
01/01/1970 |
| 2022 |
Nika Shakiba (C) |
University of British Columbia |
Subventions de démarrage pour chercheurs en début de carrière |
Wong |
Cochercheur |
Amy Wong, Bo Wang, Nika Shakiba |
120 103 |
Deciphering cell competition during iPSC differentiation towards lung epithelia |
Fibrose kystique |
Single cell tracing, barcoding, epithelial cells, iPSC, differentiation, cell competition, computational modeling, artificial intelligence |
Lung disease is the third leading cause of death worldwide with very limited treatment options for end-stage lung diseases. Generating specific cells for cell-based airway regeneration to treat degenerative airway diseases such as cystic fibrosis is a promising approach. The lung is a highly complex organ comprised of >60 cell types that collectively play a vital role in breathing, gas exchange, acid-base balance, metabolism, and immunity. To generate specific cell types for tissue regeneration therefore remains a challenge especially since the mechanisms driving lung cell development is poorly understood. Advanced single cell technologies have provided further evidence that the adult lung is much more complex and new cell types and cell states have been identified both homeostatic and diseased conditions that can change the outcome of lung functions and repair. Understanding how these cells emerge can improve targeted cell derivation processes for airway cell replacement therapies. Here, we will leverage our ability to generate airway epithelial cell types from human pluripotent stem cells (hPSC) in culture to determine how specific cells emerge and the genetic factors (fitness genes) that enable certain cells to emerge and dominate over others. Our work will identify novel gene targets to selectively enhance cell fitness and enrich for specific cell types for targeted cell-based therapies to treat airway diseases. |
01/01/1970 |
01/01/1970 |
| 2022 |
Natasha Chang (P) |
Université McGill |
Subventions de démarrage pour chercheurs en début de carrière |
Chang |
Chercheur principal |
Natasha Chang |
300 000 |
Targeting muscle stem cell dysfunction |
Muscle, muscles; dystrophie musculaire |
muscle stem cells, muscle regeneration, myogenesis, muscular dystrophy |
Duchenne muscular dystrophy (DMD) is a severely debilitating and fatal paediatric muscle disease that affects 1 in every 5,000 Canadian male births. With the help of corticosteroids, cardiac and respiratory medical care, DMD patients can now live up to 30 years of age. However, despite intense research efforts to understand the cause and progression of the disease, there still remains no effective cure for DMD. Historically, DMD has been viewed as a disease affecting the integrity of the muscle tissue, which leads to repetitive weakening and damage of the muscle fibers. However, new studies have shown that muscle stem cells, which are stem cells that reside within the muscle, are also affected in DMD. DMD stem cells do not function as normal healthy muscle stem cells, and their dysfunction plays a role in disease progression. Moreover, current DMD therapeutic strategies do not target muscle stem cells. Our research program aims to characterize muscle stem cells in DMD and to understand how they are dysfunctional. We have found that a metabolic nutrient recycling pathway is altered in DMD muscle stem cells. Our study aims to identify strategies to restore muscle stem cell function to ameliorate muscle degenerative disease. The findings from this research program will provide a proof-of-concept for targeting muscle stem cells to restore stem cell function as a therapeutic strategy for patients with DMD. |
01/01/1970 |
01/01/1970 |
| 2022 |
Nika Shakiba (P) |
University of British Columbia |
Subventions de démarrage pour chercheurs en début de carrière |
Shakiba |
Chercheur principal |
Nika Shakiba |
300 000 |
Elucidating the competitive advantage of aberrant pluripotent stem cells in suspension bioprocesses |
Bioingénierie des cellules souches |
Pluripotent stem cells, genetic variants, cell competition, synthetic biology, stem cell bioengineering, suspension culture, cell expansion |
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to understand how variants survive and thrive in culture. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at the growth of each cell. Using computational models, we will untangle these complex datasets and determine whether variants bully normal cells, using cell killing to take over the culture._x000D_
_x000D_
Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world leader in cell therapy manufacturing for regenerative medicine. |
01/01/1970 |
01/01/1970 |
| 2022 |
Julien Muffat (P) |
Hospital for Sick Children |
Subventions de démarrage pour chercheurs en début de carrière |
Muffat |
Chercheur principal |
Julien Muffat |
300 000 |
Engineering microglia to support oligodendrocyte transplants, and improve remyelination after white matter injury |
Sclérose en plaques |
Remyelination, organoid, neuroinflammation, transplantation, stem cells, microglia, oligodendrocytes |
The human brain has very limited capacity for regeneration, as seen in the progressive decline in Multiple Sclerosis One of the components destroyed in MS is the sheath that insulates the electrical wires within the brain and spinal cord. When the sheaths are gone, the wires die. The cells that form the wires cannot regenerate, but the sheaths can be repaired. If they are repaired early enough during MS, the electrical wiring will also survive, and the patient will improve. There is a population of brain immune cells, maintaining the integrity of the sheath. With age, immune cells and sheath cells lose their regenerative abilities. We can rejuvenate skin cells into stem cells, and turn them into electrical nerve cells, sheath cells, and brain immune cells. We can make a model of the electrical wiring of the brain in a culture dish. This teaches us things that animal models cannot. With this model, we will study how sheath cells contact the nerve cells, and whether the presence of immune cells helps. Later, we will induce the death of sheath cells, and observe tissue responses, mimicking aspects of MS. We will then add rejuvenated sheath cells and immune cells, to test whether either or both can restore tissue integrity and function. If, as we predict, immune cells can help sheath cells restore nerve integrity, this will pave the way for rapid application to patients, finding drugs that further improve this process, or using the patient’s own cells to restore function |
01/01/1970 |
01/01/1970 |
| 2022 |
Ly Vu (P) |
University of British Columbia |
Subventions de démarrage pour chercheurs en début de carrière |
Vu |
Chercheur principal |
Ly Vu |
300 000 |
Modulating activity of RNA regulating proteins to preserve long-term regenerative potential of Hematopoietic Stem Cells |
Cancer; greffe de moelle osseuse |
Self-renewal, Hematopoietic Stem cells (HSCs), regenerative potential, stress response |
The focus of this proposed project is umbilical cord blood-derived hematopoietic stem cells (CB-HSCs) ex vivo expansion. CB-HSCs have long been considered a key source of stem cell therapy for hematological disorders. However, the inadequate cell dose isolated from a single cord blood unit still represents a major challenge in the field. While expansion of HSCs ex vivo offers a technical solution to the limited number of cells, increasing evidence points to the reduced long-term engraftment of cultured HSCs when comparing to unexpanded HSCs. Therefore, overcoming the diminished potency of expanded HSCs is essential to push the field forward and enable the wider use of CB-HSCs in regenerative medicine. In this proposal, we aim to uncover new mediators and molecular networks controlling HSCs function under the ex vivo culture conditions. The overarching goal is to leverage the gained knowledge to implement innovative approaches to improve HSCs expansion by preserving their self-renewal capacity. In addition, mechanistic insights into the ability of HSCs to mitigate stresses and maintain their life-long repopulation capacity will enhance our understanding of stem cell biology, thus have implications in the broader stem cell research and regenerative medicine field. |
01/01/1970 |
01/01/1970 |
| 2022 |
Daniel Coutu (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de démarrage pour chercheurs en début de carrière |
Coutu |
Chercheur principal |
Daniel Coutu |
300 000 |
Pharmacological rejuvenation of skeletal stem cells for use in regenerative orthopedic surgery |
Ostéoarthrite, ostéo-arthrite |
skeletal stem cells, tissue regeneration, cellular senescence, regenerative orthopedic surgery, osteoarthritis, lineage tracing, quantitative imaging |
Chronic and debilitating conditions affecting the joints or skeleton affect over half of the Canadian population. These can be caused by trauma, normal degeneration, wear and tear, chronic inflammation or congenital malformations. The skeleton is composed of a variety of tissues including bone, cartilage, tendons, and ligaments. While it is widely assumed that stem cells are responsible for the growth, maintenance and repair of these tissues, these stem cells remain poorly characterized to date and most skeletal tissues lose regenerative capacity with age or repeated trauma. For this reason, there is an incentive to better study stem cells of the skeletal system and develop better regenerative therapies for patients. The project we propose here will study the properties of newly identified skeletal stem cell populations for their capacity to enhance skeletal tissue regeneration. We will use high-end genomics and imaging methods to study skeletal stem cells from both mouse and human tissues. We will screen pharmacological compounds for their capacity to improve tissue regeneration by stem cells using animal models of acute injury and chronic osteoarthritis. The project we propose will highlight the properties of skeletal stem cells and will be a key stepping-stone to develop and bring new therapies to patients suffering chronic, painful and debilitating orthopedic conditions. |
01/01/1970 |
01/01/1970 |
| 2022 |
Carl de Boer (P) |
University of British Columbia |
Subventions de démarrage pour chercheurs en début de carrière |
Boer |
Chercheur principal |
Carl de Boer |
300 000 |
Decoding human cis-regulatory logic in development to treat disease |
Multiples maladies |
Gene regulation, GWAS, SNP, transcription factors, heart disease, sequence design, synthetic biology |
Many common diseases, including heart disease, are thought to be caused in part by genetics. Each individual has a unique genetic makeup, which affects their disease risk in ways we do not completely understand. However, we do know that disease-associated genetic variation often lies in the DNA sequences that control when and where genes are activated. This variation causes disease by turning the genes on or off at the wrong time or in the wrong cell. Our limited understanding of the code that cells use to interpret the DNA restricts our ability to predict how genetic variation alters gene activity. Our work aims to learn this code. We will create gene regulation computer models using data from experimental measurements of synthetic DNA sequences. Our innovation lies in enabling many more sequences (tens of millions) to be measured at once, providing enough data to learn complex computer models. We are interested in heart development, and will study the cells that cause the heart to beat (cardiomyocytes) and their precursors (pluripotent cells). Once we have learned the gene regulatory code, we will use it to determine how genetics alters disease risk. Next, we will use our models to design DNA sequences that activate genes only in specific cell types that may be useful in gene therapies. This work will improve our ability to identify people at a risk of developing disease, and will enable the development of therapeutics that treat disease. |
01/01/1970 |
01/01/1970 |
| 2022 |
Maryam Faiz (P) |
University of Toronto |
Subventions de démarrage pour chercheurs en début de carrière |
Faiz |
Chercheur principal |
Maryam Faiz, Scott Yuzwa, Samer Hussein |
154 500 |
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease |
Sclérose en plaques |
Astrocyte, reprogramming, oligodendrocyte, multiple sclerosis, cuprizone, organoid, gene therapy |
Brain disease comes in many forms, all of which have grave consequences for the afflicted, their caregivers and the healthcare system. Demyelinating diseases, such as multiple sclerosis, involve the loss of oligodendrocytes (OLs), the cells that produce myelin, which is important for the rapid transmission of nerve cell signals. In addition, astrocytes, another type of brain cell, are key contributors to disease pathology and progression. We have developed a new therapeutic strategy to convert these disease-promoting astrocytes into new oligodendrocytes (called iOLs) at the site of disease in order to repair and regenerate lost myelin and OLs. A unique aspect of this therapy is that we are able to target different types of astrocytes for conversion and generate different types of OLs. This is relevant to the treatment of neurological disease as different types of OLs are lost in different diseases and different types of astrocytes are present in different diseases. Pivotal experiments aimed demonstrating : i) the conversion of specific types of astrocytes known to kill oligodendrocytes, ii) reprogramming of human astrocytes to iOLs and ii) identification and validation of new targets for generation of iOLs will be important for demonstrating the feasibility and therapeutic potential of this approach. This will support the foundation of a new company, OliGrow, with the goal of generating new therapeutics to reduce the impacts of demyelinating disease. |
01/01/1970 |
01/01/1970 |
| 2022 |
Scott Yuzwa (C) |
University of Toronto |
Subventions de démarrage pour chercheurs en début de carrière |
Faiz |
Cochercheur |
Maryam Faiz, Scott Yuzwa, Samer Hussein |
50 500 |
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease |
Sclérose en plaques |
Astrocyte, reprogramming, oligodendrocyte, multiple sclerosis, cuprizone, organoid, gene therapy |
Brain disease comes in many forms, all of which have grave consequences for the afflicted, their caregivers and the healthcare system. Demyelinating diseases, such as multiple sclerosis, involve the loss of oligodendrocytes (OLs), the cells that produce myelin, which is important for the rapid transmission of nerve cell signals. In addition, astrocytes, another type of brain cell, are key contributors to disease pathology and progression. We have developed a new therapeutic strategy to convert these disease-promoting astrocytes into new oligodendrocytes (called iOLs) at the site of disease in order to repair and regenerate lost myelin and OLs. A unique aspect of this therapy is that we are able to target different types of astrocytes for conversion and generate different types of OLs. This is relevant to the treatment of neurological disease as different types of OLs are lost in different diseases and different types of astrocytes are present in different diseases. Pivotal experiments aimed demonstrating : i) the conversion of specific types of astrocytes known to kill oligodendrocytes, ii) reprogramming of human astrocytes to iOLs and ii) identification and validation of new targets for generation of iOLs will be important for demonstrating the feasibility and therapeutic potential of this approach. This will support the foundation of a new company, OliGrow, with the goal of generating new therapeutics to reduce the impacts of demyelinating disease. |
01/01/1970 |
01/01/1970 |
| 2022 |
Samer Hussein (C) |
University of Toronto |
Subventions de démarrage pour chercheurs en début de carrière |
Faiz |
Cochercheur |
Maryam Faiz, Scott Yuzwa, Samer Hussein |
95 000 |
Direct lineage reprogramming of astrocytes to new oligodendrocytes for the treatment of demyelinating disease |
Sclérose en plaques |
Astrocyte, reprogramming, oligodendrocyte, multiple sclerosis, cuprizone, organoid, gene therapy |
Brain disease comes in many forms, all of which have grave consequences for the afflicted, their caregivers and the healthcare system. Demyelinating diseases, such as multiple sclerosis, involve the loss of oligodendrocytes (OLs), the cells that produce myelin, which is important for the rapid transmission of nerve cell signals. In addition, astrocytes, another type of brain cell, are key contributors to disease pathology and progression. We have developed a new therapeutic strategy to convert these disease-promoting astrocytes into new oligodendrocytes (called iOLs) at the site of disease in order to repair and regenerate lost myelin and OLs. A unique aspect of this therapy is that we are able to target different types of astrocytes for conversion and generate different types of OLs. This is relevant to the treatment of neurological disease as different types of OLs are lost in different diseases and different types of astrocytes are present in different diseases. Pivotal experiments aimed demonstrating : i) the conversion of specific types of astrocytes known to kill oligodendrocytes, ii) reprogramming of human astrocytes to iOLs and ii) identification and validation of new targets for generation of iOLs will be important for demonstrating the feasibility and therapeutic potential of this approach. This will support the foundation of a new company, OliGrow, with the goal of generating new therapeutics to reduce the impacts of demyelinating disease. |
01/01/1970 |
01/01/1970 |
| 2022 |
Samantha Payne (P) |
University of Guelph |
Subventions de démarrage pour chercheurs en début de carrière |
Payne |
Chercheur principal |
Samantha Payne |
273 775 |
Investigating neuron-dependent cues to promote tissue regeneration |
Régénération tissulaire |
Peripheral nervous system, progenitor cell, co-culture, proliferation, neurotransmitter |
A common response to organ or tissue damage is scarring. Aside from cosmetic considerations, scarring in organs such as the liver or lungs can lead to impaired function, disability, and reduced quality of life. Following tissue damage, scarring is caused by the abnormal activity of cells called fibroblasts, which create protein-rich stiffened matrix. In non-mammalian species, in place of scarring there is complete regeneration and restoration of function. Understanding why the response to injury differs between species will help to generate therapeutics to promote regeneration over scarring. Virtually every tissue of the body contains nerves which connect peripheral organs and tissues to the brain. In select conditions nerves can promote regeneration, but it not clearly understood how. The objective of this research project is to study the role of nerves in modulating the response to injury to develop new therapeutics to promote regeneration over scarring. We will investigate the effect of nerves on scar-forming cells to gain an understanding of why humans and other mammals form scars while non-mammals do not. This project is innovative because it will use something already present in the injury environment – nerves – and harness them towards therapeutics. Understanding how nerves prevent scar formation will help to develop treatments that will improve patient quality of life and have economic benefits to Canada in terms of lowering long-term disability costs. |
01/01/1970 |
01/01/1970 |
| 2022 |
Shinichiro Ogawa (P) |
University Health Network |
Subventions de soutien aux partenariats biotechnologiques |
Ogawa |
Chercheur principal |
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland |
331 500 |
Developing functional 3D bioprinted liver tissues with sustained immune evasion |
Maladies du foie, maladie du foie, maladie hépatique |
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues |
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Gordon Keller (C) |
University Health Network |
Subventions de soutien aux partenariats biotechnologiques |
Ogawa |
Cochercheur |
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland |
5 000 |
Developing functional 3D bioprinted liver tissues with sustained immune evasion |
Maladies du foie, maladie du foie, maladie hépatique |
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues |
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Ian McGilvray (C) |
University Health Network |
Subventions de soutien aux partenariats biotechnologiques |
Ogawa |
Cochercheur |
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland |
23 750 |
Developing functional 3D bioprinted liver tissues with sustained immune evasion |
Maladies du foie, maladie du foie, maladie hépatique |
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues |
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Sonya MacParland (C) |
University Health Network |
Subventions de soutien aux partenariats biotechnologiques |
Ogawa |
Cochercheur |
Shinichiro Ogawa, Gordon Keller, Ian McGilvray, Sonya MacParland |
39 750 |
Developing functional 3D bioprinted liver tissues with sustained immune evasion |
Maladies du foie, maladie du foie, maladie hépatique |
3D bioprinting, Human pluripotent stem cells, Hepatocytes, Immune suppression, Liver tissues |
Liver failure can only be treated with a new liver, however many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Key advances are needed before this approach is ready for patient use._x000D_
Dr. Ogawa’s team will collaborate with Aspect Biosystems Ltd. to create a working prototype of a stem cell-based treatment for liver failure, by solving three key challenges. First, they will work to increase the number of working liver cells that they can create from stem cells – several billion cells will be needed to treat a human patient. Second, they will use create 3D “bioprinted” tissues that can be implanted to restore liver function. Aspect’s collaboration will be key, as their technology can encase the liver cells in protective material to keep the patient’s immune system from attacking the transplanted cells. Finally, the team will use gene-editing techniques to remove the markers on the cell surface that cause the patient’s immune system to attack implanted cells, which should further improve the function and long-term viability of the stem-cell-based transplantation approach. _x000D_
Following this work, the team should have a working product that will be ready for testing in experimental models of liver failure and then in clinical trials. This will leverage Canadian 3D bioprinting technology and specialized scientific knowledge in the stem cell field for the benefit of Canadian patients and the economy._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Michael Underhill (P) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Underhill |
Chercheur principal |
Michael Underhill, Pamela Hoodless |
324 200 |
Novel therapeutic strategies to promote liver regeneration |
Maladies du foie, maladie du foie, maladie hépatique |
Mesenchymal progenitor, hepatic stellate cell, tissue regeneration, therapeutics, liver regeneration, fibrosis |
Mesenchymal progenitors (MPs) are a type of stem/progenitor cell, present in all tissues of our bodies. Normally, these cells are in a quiet (i.e., quiescent) state. Quiescence is an important property of many progenitors, and is critical to the healthy maintenance, renewal and regeneration of tissues. MPs exit quiescence and become activated following injury, inflammation and disease. Activated MPs have critical and diverse roles in supporting regeneration, and directly contribute to the healed tissue. Following successful regeneration, a subset of activated cells returns to a quiescent state. In other instances, activated MPs endure, contribute to tissue repair and cause fibrosis, which is associated with the accumulation of scar tissue that typically impairs organ function. Fibrosis underlies ~45% of chronic disease. Globally, chronic liver disease is a major health burden, afflicting ~844 million people. Currently, the only therapeutic option is liver transplantation, and with the shortage of livers available, there is a high unmet need for anti-fibrotic therapies. A novel genetic model will be used to explore the contribution of MPs to fibrosis, with an emphasis on the development of therapeutic approaches that enhance MP quiescence and thereby reduce fibrosis. These studies are expected to generate intellectual property and critical efficacy data, enabling the advancement of this program into the clinic to positively affect the lives of millions of patients worldwide. |
01/01/1970 |
01/04/2026 |
| 2022 |
Pamela Hoodless (C) |
BC Cancer, part of the Provincial Health Services Authority |
Subventions de soutien aux partenariats biotechnologiques |
Underhill |
Cochercheur |
Michael Underhill, Pamela Hoodless |
75 000 |
Novel therapeutic strategies to promote liver regeneration |
Maladies du foie, maladie du foie, maladie hépatique |
Mesenchymal progenitor, hepatic stellate cell, tissue regeneration, therapeutics, liver regeneration, fibrosis |
Mesenchymal progenitors (MPs) are a type of stem/progenitor cell, present in all tissues of our bodies. Normally, these cells are in a quiet (i.e., quiescent) state. Quiescence is an important property of many progenitors, and is critical to the healthy maintenance, renewal and regeneration of tissues. MPs exit quiescence and become activated following injury, inflammation and disease. Activated MPs have critical and diverse roles in supporting regeneration, and directly contribute to the healed tissue. Following successful regeneration, a subset of activated cells returns to a quiescent state. In other instances, activated MPs endure, contribute to tissue repair and cause fibrosis, which is associated with the accumulation of scar tissue that typically impairs organ function. Fibrosis underlies ~45% of chronic disease. Globally, chronic liver disease is a major health burden, afflicting ~844 million people. Currently, the only therapeutic option is liver transplantation, and with the shortage of livers available, there is a high unmet need for anti-fibrotic therapies. A novel genetic model will be used to explore the contribution of MPs to fibrosis, with an emphasis on the development of therapeutic approaches that enhance MP quiescence and thereby reduce fibrosis. These studies are expected to generate intellectual property and critical efficacy data, enabling the advancement of this program into the clinic to positively affect the lives of millions of patients worldwide. |
01/01/1970 |
01/04/2026 |
| 2022 |
Guy Sauvageau (P) |
Université de Montréal |
Subventions du programme Horizon |
Sauvageau |
Chercheur principal |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
1 282 964 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Etienne Gagnon (C) |
Université de Montréal |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
625 110 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Josée Hébert (C) |
Hôpital Maisoneuve-Rosemont, centre de recherche |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
140 000 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Ma'n Zawati (C) |
Université McGill |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
124 926 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Peter Zandstra (C) |
University of British Columbia |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
157 500 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Nika Shakiba (C) |
University of British Columbia |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
75 000 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiple Diseases |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/04/2022 |
31/01/2025 |
| 2022 |
Philippe Roux (C) |
Université de Montréal |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
117 500 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Vincent-Philippe Lavallée (C) |
Centre Hospitalier Universitaire Sainte-Justine |
Subventions du programme Horizon |
Sauvageau |
Cochercheur |
Guy Sauvageau, Etienne Gagnon, Josée Hébert, Ma'n Zawati, Peter Zandstra, Nika Shakiba, Philippe Roux, Vincent-Philippe Lavallée |
477 000 |
Engineered hematopoietic stem cells (eHSCs) as vehicles for next generation therapies |
Multiples maladies |
Hematopoietic Stem Cells (HSCs), Chimeric Antigen Receptors (CAR), Stem Cell Engineering, Cellular Immunotherapy |
Modern cancer therapies increasingly rely on antibody-based drugs or genetically engineered immune cells that are programmed towards recognizing specific proteins on the cell surface of cancerous cells while not attacking their healthy counterparts. For many aggressive blood cancers (like AML), leukemic and healthy blood cells express largely similar proteins on their surface. This poses an important challenge for the development of selective immune-based treatments for these patients. _x000D_
To address this limitation, we will identify proteins with robust expression on leukemia cells that, at the same time, are functionally dispensable for transplantable blood stem cells. For these proteins, we will downregulate their expression in genetically engineered blood stem cell grafts. With this approach, we hope to improve the selective killing of leukemia cells while sparing the normal blood system regenerated from these engineered stem cell transplants. _x000D_
In addition, we will establish an improved delivery of genetically engineered anti-leukemia immune cells into leukemia patients. Specifically, instead of engineering these relatively short-lived cells directly, we propose to modify blood stem cells, since these will regenerate engineered immune cells for life. This alternative delivery of engineered anti-leukemia immune cells requires a significant redesign of the underlying genetic engineering approach yet is expected to vastly improve therapeutic prospects of leukemia patients._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
James Shapiro (P) |
University of Alberta |
Subventions du programme Horizon |
Shapiro |
Chercheur principal |
James Shapiro, Michael Kallos, Timothy Kieffer |
2 450 238 |
Autologous iPSC-Islets for Personalized Diabetes Therapy: a First-in-Human Implantation and Scale-up Manufacturing |
Diabète |
Diabetes, iPSC, pancreatic islets, cell replacement therapy, islet transplantation, subcutaneous implantation, bioreactor scale-up |
Diabetes is caused by the lack of insulin, a hormone produced by the islet beta-cells in the pancreas that regulates blood sugar. Chronically high blood sugar can cause complications like blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is lifesaving but is not a cure. Islet transplant has been successful in regulating blood sugar levels in some patients with T1D; however, it requires life-long antirejection drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, we will address these challenges by developing a stem-cell based therapy to replace the damaged beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after resection of the pancreas. We propose to make new islet beta cells from patients’ own blood cells, so that the cells will be accepted by the immune system and no anti-rejection drugs will be needed. In this project, a small dose of the generated self-islets will be implanted under the patient’s skin. We will also try to scale-up the manufacturing of the self-islets to reach a larger dose to help blood sugar control. We anticipate that this project will 1) establish safety of the manufactured self-islets and that they can produce insulin and 2) demonstrate the feasibility of scaling up manufacturing without compromising cell quality. |
01/01/1970 |
01/01/1970 |
| 2022 |
Michael Kallos (C) |
University of Calgary |
Subventions du programme Horizon |
Shapiro |
Cochercheur |
James Shapiro, Michael Kallos, Timothy Kieffer |
298 825 |
Autologous iPSC-Islets for Personalized Diabetes Therapy: a First-in-Human Implantation and Scale-up Manufacturing |
Diabète |
Diabetes, iPSC, pancreatic islets, cell replacement therapy, islet transplantation, subcutaneous implantation, bioreactor scale-up |
Diabetes is caused by the lack of insulin, a hormone produced by the islet beta-cells in the pancreas that regulates blood sugar. Chronically high blood sugar can cause complications like blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is lifesaving but is not a cure. Islet transplant has been successful in regulating blood sugar levels in some patients with T1D; however, it requires life-long antirejection drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, we will address these challenges by developing a stem-cell based therapy to replace the damaged beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after resection of the pancreas. We propose to make new islet beta cells from patients’ own blood cells, so that the cells will be accepted by the immune system and no anti-rejection drugs will be needed. In this project, a small dose of the generated self-islets will be implanted under the patient’s skin. We will also try to scale-up the manufacturing of the self-islets to reach a larger dose to help blood sugar control. We anticipate that this project will 1) establish safety of the manufactured self-islets and that they can produce insulin and 2) demonstrate the feasibility of scaling up manufacturing without compromising cell quality. |
01/01/1970 |
01/01/1970 |
| 2022 |
Timothy Kieffer (C) |
University of British Columbia |
Subventions du programme Horizon |
Shapiro |
Cochercheur |
James Shapiro, Michael Kallos, Timothy Kieffer |
244 333 |
Autologous iPSC-Islets for Personalized Diabetes Therapy: a First-in-Human Implantation and Scale-up Manufacturing |
Diabète |
Diabetes, iPSC, pancreatic islets, cell replacement therapy, islet transplantation, subcutaneous implantation, bioreactor scale-up |
Diabetes is caused by the lack of insulin, a hormone produced by the islet beta-cells in the pancreas that regulates blood sugar. Chronically high blood sugar can cause complications like blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is lifesaving but is not a cure. Islet transplant has been successful in regulating blood sugar levels in some patients with T1D; however, it requires life-long antirejection drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, we will address these challenges by developing a stem-cell based therapy to replace the damaged beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after resection of the pancreas. We propose to make new islet beta cells from patients’ own blood cells, so that the cells will be accepted by the immune system and no anti-rejection drugs will be needed. In this project, a small dose of the generated self-islets will be implanted under the patient’s skin. We will also try to scale-up the manufacturing of the self-islets to reach a larger dose to help blood sugar control. We anticipate that this project will 1) establish safety of the manufactured self-islets and that they can produce insulin and 2) demonstrate the feasibility of scaling up manufacturing without compromising cell quality. |
01/01/1970 |
01/01/1970 |
| 2022 |
Sara Vasconcelos (P) |
University Health Network |
Subventions du programme Horizon |
Vasconcelos |
Chercheur principal |
Sara Vasconcelos, Gregory Korbutt, Michael Laflamme |
2 270 110 |
Advancing microvessel-based cardiac regeneration into a large pre-clinical animal model |
Cardiaque; infarctus du myocarde |
pig, myocardial infarction, microvessels, cell-based therapies, revascularization, cardiac regeneration |
Cell transplantation can be a cure for several diseases, including but not limited to heart attacks. However, for cells to survive transplantation and regenerate organs they need immediate access to oxygen and nutrients, which are delivered via blood vessels. So, for any cell therapy to work, we need to create new blood vessels to feed the transplanted cells. Unfortunately, most attempts at making new blood vessels for organ regeneration have failed._x000D_
Our group has shown for the first time that recycling blood vessels from fat to support the survival of transplanted cells leads to cell survival and improves organ function in a small animal model._x000D_
Here we will advance this work into large animal model in the pig that will generate essential data necessary to advance this therapy into clinical trials in humans._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Gregory Korbutt (C) |
University of Alberta |
Subventions du programme Horizon |
Vasconcelos |
Cochercheur |
Sara Vasconcelos, Gregory Korbutt, Michael Laflamme |
100 800 |
Advancing microvessel-based cardiac regeneration into a large pre-clinical animal model |
Cardiaque; infarctus du myocarde |
pig, myocardial infarction, microvessels, cell-based therapies, revascularization, cardiac regeneration |
Cell transplantation can be a cure for several diseases, including but not limited to heart attacks. However, for cells to survive transplantation and regenerate organs they need immediate access to oxygen and nutrients, which are delivered via blood vessels. So, for any cell therapy to work, we need to create new blood vessels to feed the transplanted cells. Unfortunately, most attempts at making new blood vessels for organ regeneration have failed._x000D_
Our group has shown for the first time that recycling blood vessels from fat to support the survival of transplanted cells leads to cell survival and improves organ function in a small animal model._x000D_
Here we will advance this work into large animal model in the pig that will generate essential data necessary to advance this therapy into clinical trials in humans._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Michael Laflamme (C) |
University Health Network |
Subventions du programme Horizon |
Vasconcelos |
Cochercheur |
Sara Vasconcelos, Gregory Korbutt, Michael Laflamme |
629 090 |
Advancing microvessel-based cardiac regeneration into a large pre-clinical animal model |
Cardiaque; infarctus du myocarde |
pig, myocardial infarction, microvessels, cell-based therapies, revascularization, cardiac regeneration |
Cell transplantation can be a cure for several diseases, including but not limited to heart attacks. However, for cells to survive transplantation and regenerate organs they need immediate access to oxygen and nutrients, which are delivered via blood vessels. So, for any cell therapy to work, we need to create new blood vessels to feed the transplanted cells. Unfortunately, most attempts at making new blood vessels for organ regeneration have failed._x000D_
Our group has shown for the first time that recycling blood vessels from fat to support the survival of transplanted cells leads to cell survival and improves organ function in a small animal model._x000D_
Here we will advance this work into large animal model in the pig that will generate essential data necessary to advance this therapy into clinical trials in humans._x000D_ |
01/01/1970 |
01/01/1970 |
| 2022 |
Juan Carlos Zúñiga-Pflücker (C) |
Sunnybrook Health Sciences Centre |
Subventions de soutien aux projects à fort impact |
Keller |
Cochercheur |
Gordon Keller, Juan Carlos Zúñiga-Pflücker |
100 000 |
Novel human pluripotent stem cell-derived hematopoietic cell therapy |
Multiples maladies |
Human pluripotent stem cells, hematopoietic stem cells, T cell progenitors, neutrophil progenitors, cell therapy |
Blood disorders, such as leukemia, can be treated or even cured by bone marrow transplantation. The success of this therapy is due to the presence of blood-forming stem cells in bone marrow, that following transplantation, create a new blood-forming system in the patient. While successful, this therapy is limited to patients that have a matched bone marrow (stem cell) donor. A second challenge is that the transplanted stem cells take time to regenerate cells of the immune system , specifically those cells known as T-cells. This delay can leave transplant patients susceptible to life threatening infections. _x000D_
_x000D_
Our research proposed seeks to address these limitations by producing blood-forming stem cells and T cell progenitors in the lab from a specialized type of stem cell known as a human pluripotent stem cell (hPSCs). The proposed experiments build on recent findings from Dr. Keller’s lab showing that it is possible to generate blood forming progenitors from hPSCs. We will optimize the development of these progenitors and demonstrate that they are indeed human blood-forming stem cells. We will also generate T cell progenitors from hPSCs that can rapidly make T cells following transplantation and demonstrate that they can generate function T cells in mice. A successful outcome will move us one step closer to developing novel cell therapies to treat patients with leukemia and other blood cell disorders who currently are unable to receive a bone marrow transplant. |
01/01/1970 |
01/04/2026 |
| 2022 |
Gordon Keller (P) |
University Health Network |
Subventions de soutien aux projects à fort impact |
Keller |
Chercheur principal |
Gordon Keller, Juan Carlos Zúñiga-Pflücker |
149 820 |
Novel human pluripotent stem cell-derived hematopoietic cell therapy |
Multiples maladies |
Human pluripotent stem cells, hematopoietic stem cells, T cell progenitors, neutrophil progenitors, cell therapy |
Blood disorders, such as leukemia, can be treated or even cured by bone marrow transplantation. The success of this therapy is due to the presence of blood-forming stem cells in bone marrow, that following transplantation, create a new blood-forming system in the patient. While successful, this therapy is limited to patients that have a matched bone marrow (stem cell) donor. A second challenge is that the transplanted stem cells take time to regenerate cells of the immune system , specifically those cells known as T-cells. This delay can leave transplant patients susceptible to life threatening infections. _x000D_
_x000D_
Our research proposed seeks to address these limitations by producing blood-forming stem cells and T cell progenitors in the lab from a specialized type of stem cell known as a human pluripotent stem cell (hPSCs). The proposed experiments build on recent findings from Dr. Keller’s lab showing that it is possible to generate blood forming progenitors from hPSCs. We will optimize the development of these progenitors and demonstrate that they are indeed human blood-forming stem cells. We will also generate T cell progenitors from hPSCs that can rapidly make T cells following transplantation and demonstrate that they can generate function T cells in mice. A successful outcome will move us one step closer to developing novel cell therapies to treat patients with leukemia and other blood cell disorders who currently are unable to receive a bone marrow transplant. |
01/01/1970 |
01/04/2026 |
| 2022 |
Martin Levesque (P) |
Université Laval |
Subventions de soutien aux projects à fort impact |
Levesque |
Chercheur principal |
Martin Levesque, Samer Hussein |
183 000 |
Repairing the dopaminergic circuits in Parkinson disease using synucleinopathy resistant neurones grafting |
Maladie de Parkinson |
Parkinson, iPSC, mouse model, alpha-synuclein, cell transplantation, brain organoid, dopamine neurons. |
Parkinson's disease is a chronic brain disorder, characterized by the accumulation of toxic protein aggregates and the degeneration of dopamine producing neurons. Cell replacement therapy aims to restore function in the body by replacing lost, or dysfunctional cells by healthy ones. Although recent progress facilitates cell replacement therapy for Parkinson's disease, there are still hurdles to overcome. One major challenge is the survival of the grafted neurons in a brain environment containing these toxic protein aggregates. _x000D_
_x000D_
Our main objective is to develop strategies to promote survival of transplanted dopamine neurons to efficiently restore the dopamine deficiencies. Our aims are designed to propose a solution to an important barrier of the effectiveness of cell transplantation i.e. enhance survival of dopamine neuron engraftment in the pathological brain. Our team provides a uniquely suited combination of expertise in cell transplantation and Parkinson’s disease models to carry the proposed work to successful completion. The work will be carried out in preclinical models of Parkinson’s disease and will contribute to a significant amelioration of cell replacement therapies._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Samer Hussein (C) |
Université Laval |
Subventions de soutien aux projects à fort impact |
Levesque |
Cochercheur |
Martin Levesque, Samer Hussein |
67 000 |
Repairing the dopaminergic circuits in Parkinson disease using synucleinopathy resistant neurones grafting |
Maladie de Parkinson |
Parkinson, iPSC, mouse model, alpha-synuclein, cell transplantation, brain organoid, dopamine neurons. |
Parkinson's disease is a chronic brain disorder, characterized by the accumulation of toxic protein aggregates and the degeneration of dopamine producing neurons. Cell replacement therapy aims to restore function in the body by replacing lost, or dysfunctional cells by healthy ones. Although recent progress facilitates cell replacement therapy for Parkinson's disease, there are still hurdles to overcome. One major challenge is the survival of the grafted neurons in a brain environment containing these toxic protein aggregates. _x000D_
_x000D_
Our main objective is to develop strategies to promote survival of transplanted dopamine neurons to efficiently restore the dopamine deficiencies. Our aims are designed to propose a solution to an important barrier of the effectiveness of cell transplantation i.e. enhance survival of dopamine neuron engraftment in the pathological brain. Our team provides a uniquely suited combination of expertise in cell transplantation and Parkinson’s disease models to carry the proposed work to successful completion. The work will be carried out in preclinical models of Parkinson’s disease and will contribute to a significant amelioration of cell replacement therapies._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Milica Radisic (P) |
University Health Network |
Subventions de soutien aux projects à fort impact |
Radisic |
Chercheur principal |
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman |
145 000 |
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration |
Cardiaque; infarctus du myocarde |
cardiac tissue engineering, polymer, cell delivery, macrophage, cardiomyocyte, fibroblast, pluripotent stem cell, integration, myocardium |
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack. |
01/01/1970 |
01/04/2026 |
| 2022 |
Gordon Keller (C) |
University Health Network |
Subventions de soutien aux projects à fort impact |
Radisic |
Cochercheur |
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman |
30 000 |
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration |
Cardiaque; infarctus du myocarde |
cardiac tissue engineering, polymer, cell delivery, macrophage, cardiomyocyte, fibroblast, pluripotent stem cell, integration, myocardium |
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack. |
01/01/1970 |
01/04/2026 |
| 2022 |
Michael Laflamme (C) |
University Health Network |
Subventions de soutien aux projects à fort impact |
Radisic |
Cochercheur |
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman |
10 000 |
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration |
Cardiaque; infarctus du myocarde |
cardiac tissue engineering, polymer, cell delivery, macrophage, cardiomyocyte, fibroblast, pluripotent stem cell, integration, myocardium |
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack. |
01/01/1970 |
01/04/2026 |
| 2022 |
Slava Epelman (C) |
University Health Network |
Subventions de soutien aux projects à fort impact |
Radisic |
Cochercheur |
Milica Radisic, Gordon Keller, Michael Laflamme, Slava Epelman |
65 000 |
Stem cell derived resident cardiac macrophages in designer polymers for cardiac repair and regeneration |
Cardiaque; infarctus du myocarde |
cardiac tissue engineering, polymer, cell delivery, macrophage, cardiomyocyte, fibroblast, pluripotent stem cell, integration, myocardium |
Heart attack can lead to the loss of a billion of beating heart cells within minutes. The body cannot replace these cells on its own, thus injection of stem cell derived heart cells has been explored. Although the results are promising, the injected cells transiently cause dangerous arrhythmias, and they cannot fully integrate with the host tissue. We hypothesize that this is due to the use of pure beating heart cells without important supporting cells. One such supporting cell is a macrophage, a cell of the immune system. Their subset populates our tissues during the earliest stages of our development in the womb. They are responsible for the healing and regeneration of our tissues. Yet, they are excluded from heart therapy since scientists do not know how to produce them. Here, we will first study markers of these immune cells and how they change from birth to adulthood, then we will derive their primitive version from human stem cells. Yet, for them to be able to orchestrate healing of the heart, first they need to be programmed in a heart environment, as they do in a developing baby. We will achieve that by introducing them to a heart-on-a-chip platform, enabling them to acquire heart regeneration capability. This knowledge will enable us to create heart microtissues with just the right combination of beating and supporting cells, that look and beat like a real heart muscle. We will use these microtissues to regenerate the heart in a rat model of a heart attack. |
01/01/1970 |
01/04/2026 |
| 2022 |
Lucie Germain (P) |
Université Laval |
Subventions de soutien aux projects à fort impact |
Germain |
Chercheur principal |
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin |
223 272 |
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa |
Peau; épidermolyse bulleuse |
Skin stem cells, Tissue engineering, Gene therapy, Dystrophic Epidermolysis Bullosa, Rare diseases, skin substitute |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/01/1970 |
01/04/2026 |
| 2022 |
Bartha Knoppers (C) |
Université McGill |
Subventions de soutien aux projects à fort impact |
Germain |
Cochercheur |
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin |
10 000 |
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa |
Peau; épidermolyse bulleuse |
Skin stem cells, Tissue engineering, Gene therapy, Dystrophic Epidermolysis Bullosa, Rare diseases, skin substitute |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/01/1970 |
01/04/2026 |
| 2022 |
Elena Pope (C) |
Hospital for Sick Children |
Subventions de soutien aux projects à fort impact |
Germain |
Cochercheur |
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin |
5 000 |
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa |
Peau; épidermolyse bulleuse |
Skin stem cells, Tissue engineering, Gene therapy, Dystrophic Epidermolysis Bullosa, Rare diseases, skin substitute |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/01/1970 |
01/04/2026 |
| 2022 |
Manuel Caruso (C) |
Université Laval |
Subventions de soutien aux projects à fort impact |
Germain |
Cochercheur |
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin |
7 200 |
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa |
Peau; épidermolyse bulleuse |
Skin stem cells, Tissue engineering, Gene therapy, Dystrophic Epidermolysis Bullosa, Rare diseases, skin substitute |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/01/1970 |
01/04/2026 |
| 2022 |
Véronique Moulin (C) |
Université Laval |
Subventions de soutien aux projects à fort impact |
Germain |
Cochercheur |
Lucie Germain, Bartha Knoppers, Elena Pope, Manuel Caruso, Véronique Moulin |
4 528 |
Combining tissue-engineered skin with ex vivo gene therapy correction to develop a treatment for epidermolysis bullosa |
Peau; épidermolyse bulleuse |
Skin stem cells, Tissue engineering, Gene therapy, Dystrophic Epidermolysis Bullosa, Rare diseases, skin substitute |
Recessive dystrophic epidermolysis bullosa (RDEB) is a disease affecting the skin and mucosa. RDEB patients have very fragile skin due to a mutation in the collagen 7 gene. There is no cure for EB. The only option is to treat the recurrent wounds with daily care and bandages. Patients experience pain, suffering and poor quality of life. _x000D_
_x000D_
The LOEX/CHU de Québec-Université Laval, a leader in the autologous self-assembled skin substitute (SASS) therapy, using cultured stem cells for the treatment of burn patients, has initiated research studies to find a treatment for RDEB. Our interdisciplinary team brings together experts in : stem cells and tissue engineering; gene therapy; socio-ethical and legal issues; a pediatric dermatologist directing the largest Canadian EB clinic and many research professionals. _x000D_
_x000D_
The objective of the present proposal is to complete the steps necessary for the translation, from the laboratory to the clinic, of our new therapeutic approach combining gene therapy and tissue engineering. _x000D_
_x000D_
Ultimately, our goal is to develop a definitive treatment for RDEB. Without a cure, RDEB patients have recurrent wounds. The annual costs for specialized bandages is very expensive. This rare disease impacts on the quality of life of patients and their families. Therefore, this new treatment, if proven successful, could change lives of Canadian patients by improving skin stability and preventing recurring wounds. |
01/01/1970 |
01/04/2026 |
| 2022 |
Bernard Thébaud (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien aux projects à fort impact |
Thébaud |
Chercheur principal |
Bernard Thébaud |
249 976 |
Ironman – Improved Respiratory Outcome of Newborns with Modified Angiogenic Nanovesicles |
Hypertension pulmonaire |
Regenerative medicine, Cell therapy, Endothelial progenitor cells, Extra-cellular vesicles, Lung injury, Newborn, Pulmonary hypertension |
High blood pressure in the lungs (pulmonary hypertension, PH) complicates lung diseases in babies with overly small lungs. PH doubles the risk of death, and survivors have long-term health problems that can reach into adulthood. Today, there is no effective treatment for severe PH. Our lab showed that specific cells (endothelial progenitor cells or EPCs) can make new blood vessels and stimulate lung growth and lower PH. These cells act like “smart local pharmacies” by releasing tiny particles (extra-cellular vesicles or EV) that contain factors to instruct new blood vessels to grow. We are using a new, induced pluripotent-derived EPC that can be easily and consistently produced in very high quantities. We will test if the EVs from these cells are safe and effective in lab experiments. If so, our innovation will bring a breakthrough treatment that will save lives and improving the quality of life of babies with PH. Our discovery will deliver economic, social and health benefits for Canadians and patients around the world that suffer from diseases with low blood supply such as heart attack, stroke or preeclampsia (high blood pressure in pregnant women that puts the life of both mother and baby at risk; it often leads to a C-section and preterm delivery). This new cell product has potential for commercialization and job creation. It has already led our partner Dr. Yoder to create a company (Vascugen) with the goal of manufacturing a new cell product to be used in patients. |
01/01/1970 |
01/04/2026 |
| 2022 |
Lauren Flynn (P) |
University of Western Ontario |
Subventions de soutien aux projects à fort impact |
Flynn |
Chercheur principal |
Lauren Flynn, John Ronald |
230 000 |
Delivery of adipose-derived stromal cells within novel cell-assembled bioscaffolds for the treatment of chronic wounds |
Peau; cicatrisation |
Wound healing, skin regeneration, cell therapies, adipose-derived stromal cells, extracellular matrix, bioscaffold, pre-clinical models. |
Chronic or non-healing skin wounds are a significant and growing clinical problem that occurs frequently in diabetics, individuals with vascular disease, and patients who are elderly or have mobility restrictions, negatively affecting their overall health and quality of life. Treating these wounds is costly and places a substantial burden on the Canadian healthcare system. Unfortunately, current wound dressings fail to address the underlying biological dysfunction within the wound bed, resulting in unpredictable outcomes and treatment times that often extend beyond 20 weeks. In cases where the wound fails to heal, amputation of the affected limb may be required. The proposed research addresses the critical need for new chronic wound treatments. Our team has designed novel cell therapies derived from human fat discarded as surgical waste that can naturally promote blood vessel formation and soft tissue regeneration. In the current project, our interdisciplinary team of experts will perform pre-clinical testing using established mouse and pig models to validate that our patented cell therapy platform can robustly and reproducibly stimulate healing. This data will allow us to advance towards clinical trials in humans and demonstrate proof-of-concept of our promising technology to potential industry partners in the wound care sector who could aid in commercialization and clinical translation, helping to position Canada as a leader in the advanced wound care field. |
01/01/1970 |
01/04/2026 |
| 2022 |
John Ronald (C) |
University of Western Ontario |
Subventions de soutien aux projects à fort impact |
Flynn |
Cochercheur |
Lauren Flynn, John Ronald |
20 000 |
Delivery of adipose-derived stromal cells within novel cell-assembled bioscaffolds for the treatment of chronic wounds |
Peau; cicatrisation |
Wound healing, skin regeneration, cell therapies, adipose-derived stromal cells, extracellular matrix, bioscaffold, pre-clinical models. |
Chronic or non-healing skin wounds are a significant and growing clinical problem that occurs frequently in diabetics, individuals with vascular disease, and patients who are elderly or have mobility restrictions, negatively affecting their overall health and quality of life. Treating these wounds is costly and places a substantial burden on the Canadian healthcare system. Unfortunately, current wound dressings fail to address the underlying biological dysfunction within the wound bed, resulting in unpredictable outcomes and treatment times that often extend beyond 20 weeks. In cases where the wound fails to heal, amputation of the affected limb may be required. The proposed research addresses the critical need for new chronic wound treatments. Our team has designed novel cell therapies derived from human fat discarded as surgical waste that can naturally promote blood vessel formation and soft tissue regeneration. In the current project, our interdisciplinary team of experts will perform pre-clinical testing using established mouse and pig models to validate that our patented cell therapy platform can robustly and reproducibly stimulate healing. This data will allow us to advance towards clinical trials in humans and demonstrate proof-of-concept of our promising technology to potential industry partners in the wound care sector who could aid in commercialization and clinical translation, helping to position Canada as a leader in the advanced wound care field. |
01/01/1970 |
01/04/2026 |
| 2022 |
Molly Shoichet (P) |
University of Toronto |
Subventions de soutien aux projects à fort impact |
Shoichet |
Chercheur principal |
Molly Shoichet, Andras Nagy, Cindi Morshead |
110 000 |
Regenerating the Stroke Injured Brain by Modulating the Glial Scar and Enhancing Neuroplasticity |
Accident vasculaire cérébral; AVC |
Brain, stroke, glial scar, neural stem cells, chondroitinase abc, local delivery, regeneration |
Stroke is devastating. There is minimal warning and after a stroke, there are few therapeutic strategies other than surgical and rehabilitation. There is currently no way to overcome the tissue and functional damage in the brain after stroke. To achieve success in this complex problem of regenerating the brain, we propose a series of innovative and inventive strategies. _x000D_
1. We will locally deliver an enzyme that will breakdown the chemical and physical barriers that exist in the brain after stroke. _x000D_
We invented a new enzyme and a new way to deliver it. As the enzyme is very fragile, we designed a more stable version (that we have now patented). As typical protein delivery strategies are unsuitable for this particular enzyme, we invented a new way to deliver it locally and for a sustained period. Importantly, this enzyme has been shown to modulate the immune response and promote plasticity. _x000D_
2. We will inject stem cell derived nerve cells to replace and/or repair those lost due damage._x000D_
We designed human progenitor cells that differentiate to brain cells and have the capacity to repair the stroke-injured brain. We have already had some success with their delivery in our patented hydrogel and now propose to co-deliver these cells with our novel enzyme. In this way, the enzyme will breakdown the inhibitory environment and the cells will integrate more effectively with the brain tissue, thereby achieving greater tissue and behavioural repair._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Andras Nagy (C) |
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital |
Subventions de soutien aux projects à fort impact |
Shoichet |
Cochercheur |
Molly Shoichet, Andras Nagy, Cindi Morshead |
30 000 |
Regenerating the Stroke Injured Brain by Modulating the Glial Scar and Enhancing Neuroplasticity |
Accident vasculaire cérébral; AVC |
Brain, stroke, glial scar, neural stem cells, chondroitinase abc, local delivery, regeneration |
Stroke is devastating. There is minimal warning and after a stroke, there are few therapeutic strategies other than surgical and rehabilitation. There is currently no way to overcome the tissue and functional damage in the brain after stroke. To achieve success in this complex problem of regenerating the brain, we propose a series of innovative and inventive strategies. _x000D_
1. We will locally deliver an enzyme that will breakdown the chemical and physical barriers that exist in the brain after stroke. _x000D_
We invented a new enzyme and a new way to deliver it. As the enzyme is very fragile, we designed a more stable version (that we have now patented). As typical protein delivery strategies are unsuitable for this particular enzyme, we invented a new way to deliver it locally and for a sustained period. Importantly, this enzyme has been shown to modulate the immune response and promote plasticity. _x000D_
2. We will inject stem cell derived nerve cells to replace and/or repair those lost due damage._x000D_
We designed human progenitor cells that differentiate to brain cells and have the capacity to repair the stroke-injured brain. We have already had some success with their delivery in our patented hydrogel and now propose to co-deliver these cells with our novel enzyme. In this way, the enzyme will breakdown the inhibitory environment and the cells will integrate more effectively with the brain tissue, thereby achieving greater tissue and behavioural repair._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Cindi Morshead (C) |
University of Toronto |
Subventions de soutien aux projects à fort impact |
Shoichet |
Cochercheur |
Molly Shoichet, Andras Nagy, Cindi Morshead |
110 000 |
Regenerating the Stroke Injured Brain by Modulating the Glial Scar and Enhancing Neuroplasticity |
Accident vasculaire cérébral; AVC |
Brain, stroke, glial scar, neural stem cells, chondroitinase abc, local delivery, regeneration |
Stroke is devastating. There is minimal warning and after a stroke, there are few therapeutic strategies other than surgical and rehabilitation. There is currently no way to overcome the tissue and functional damage in the brain after stroke. To achieve success in this complex problem of regenerating the brain, we propose a series of innovative and inventive strategies. _x000D_
1. We will locally deliver an enzyme that will breakdown the chemical and physical barriers that exist in the brain after stroke. _x000D_
We invented a new enzyme and a new way to deliver it. As the enzyme is very fragile, we designed a more stable version (that we have now patented). As typical protein delivery strategies are unsuitable for this particular enzyme, we invented a new way to deliver it locally and for a sustained period. Importantly, this enzyme has been shown to modulate the immune response and promote plasticity. _x000D_
2. We will inject stem cell derived nerve cells to replace and/or repair those lost due damage._x000D_
We designed human progenitor cells that differentiate to brain cells and have the capacity to repair the stroke-injured brain. We have already had some success with their delivery in our patented hydrogel and now propose to co-deliver these cells with our novel enzyme. In this way, the enzyme will breakdown the inhibitory environment and the cells will integrate more effectively with the brain tissue, thereby achieving greater tissue and behavioural repair._x000D_ |
01/01/1970 |
01/04/2026 |
| 2022 |
Pamela Hoodless (P) |
University of British Columbia |
Subventions de soutien aux projects à fort impact |
Hoodless |
Chercheur principal |
Pamela Hoodless |
250 000 |
Pathways of Cell Identity in Human Liver Organoids |
Multiples maladies |
Liver, Organoids, Human pluripotent stem cells, Signal Transduction, Cell-cell interactions, Lineage Tracing |
Liver disorders re a leading cause of death worldwide. Non-alcoholic fatty liver disease affects over 7 million Canadians and liver cancer is fastest rising cancer in Canada. Current treatments for chronic liver disease focus on slowing progression and minimizing complications, such as hypertension. Liver transplantation is a potential cure, but is dependent on donor availability._x000D_
_x000D_
Recent advances in the generation of hepatocytes, the main functional cell in the liver, from human pluripotent stem cells (hPSCs) have excited researchers by providing a potential source of cells for transplants, drug testing and bioarticial liver devices. Current methods of making hepatocytes in a dish from hPSCs do not produce fully functional hepatocytes. Moreover, other types of cells that are needed for a proper functioning liver are rarely included. To improve methods, we need to better understand how heaptocytes interact with other cell types during development to create a fully functional liver._x000D_
_x000D_
Our project will generate livers from hPSCs using multi-cellular, 3D organoid cultures, often called 'mini-livers'. Importantly, these organoids contain many of the different types of cells necessary for liver functions. We will use state-of-the-art methods to understand how different cells are related in organoids and will explore the cellular environment which drives liver development. Our project will address how close organoids are to normal liver development and how they may be improved. |
01/01/1970 |
01/04/2026 |
| 2022 |
Karun Singh (P) |
University Health Network |
Subventions de soutien aux projects à fort impact |
Singh |
Chercheur principal |
Karun Singh, Sarah Wootton |
235 000 |
Gene therapy to restore neural connectivity in neurodevelopmental disorders associated with a CNV microdeletion |
Multiples maladies |
Gene therapy, neural connectivity, 3D brain organoids, neurodevelopmental disorders, regeneration, disease modelling, CNV deletions |
The 15q13.3 deletion is a neurodevelopmental disorder (NDD) that manifests early during postnatal life and is associated with epilepsy, schizophrenia, autism spectrum disorder and developmental delay. It is a genetic disorder caused by the loss of a small piece of genetic material (DNA), and is recurrently found in genetic studies, occurring in 1 in 2500-5000 individuals. The genomic region affected typically contains ~10 genes. There are no treatments that reverse or cure the symptoms and impairments experienced by individuals, which cause life-long disabilities. We recently identified that one of the ten genes (OTUD7A) in this genetic region may be responsible to for mediating a major portion of the clinical outcomes associated with this deletion. To understand how OTUD7A contributes to abnormal brain function, we performed a novel screen to identify which proteins interact with OTUD7A and revealed that it regulates signaling molecules through a process named protein homeostasis, which is the regulation of protein levels. In this project, we will examine whether the loss of OTUD7A function impairs axonal and synaptic development using patient stem cell-derived neural cells as models. We hypothesize that abnormal protein homeostasis of targets of OTUD7A contributes to defective synaptic development and neural plasticity, its. We will also test a gene therapy strategy to restore OTUD7A function and regenerate defective neural circuits in patient-derived neural cells. |
01/01/1970 |
01/04/2026 |
| 2022 |
Sarah Wootton (C) |
University of Guelph |
Subventions de soutien aux projects à fort impact |
Singh |
Cochercheur |
Karun Singh, Sarah Wootton |
15 000 |
Gene therapy to restore neural connectivity in neurodevelopmental disorders associated with a CNV microdeletion |
Multiples maladies |
Gene therapy, neural connectivity, 3D brain organoids, neurodevelopmental disorders, regeneration, disease modelling, CNV deletions |
The 15q13.3 deletion is a neurodevelopmental disorder (NDD) that manifests early during postnatal life and is associated with epilepsy, schizophrenia, autism spectrum disorder and developmental delay. It is a genetic disorder caused by the loss of a small piece of genetic material (DNA), and is recurrently found in genetic studies, occurring in 1 in 2500-5000 individuals. The genomic region affected typically contains ~10 genes. There are no treatments that reverse or cure the symptoms and impairments experienced by individuals, which cause life-long disabilities. We recently identified that one of the ten genes (OTUD7A) in this genetic region may be responsible to for mediating a major portion of the clinical outcomes associated with this deletion. To understand how OTUD7A contributes to abnormal brain function, we performed a novel screen to identify which proteins interact with OTUD7A and revealed that it regulates signaling molecules through a process named protein homeostasis, which is the regulation of protein levels. In this project, we will examine whether the loss of OTUD7A function impairs axonal and synaptic development using patient stem cell-derived neural cells as models. We hypothesize that abnormal protein homeostasis of targets of OTUD7A contributes to defective synaptic development and neural plasticity, its. We will also test a gene therapy strategy to restore OTUD7A function and regenerate defective neural circuits in patient-derived neural cells. |
01/01/1970 |
01/04/2026 |
| 2022 |
Vardit Ravitsky (P) |
Université de Montréal |
Subventions du programme Applications et Société |
Ravitsky |
Chercheur principal |
Vardit Ravitsky, Jonathan Kimmelman, Ma’n Zawati |
136 415 |
Responsible Pathways for Pediatric Cell Therapies |
Multiples maladies |
Cell therapy; clinical trials; first-in-human trials; ethics; law; children’s rights; minors |
Cell therapies hold much promise for the treatment and prevention of disease. Minors are frequently the focus of such interventions, meant to prevent or investigate the expression of early onset diseases. But their inclusion as research participants in clinical trials requires unique ethical and legal protections. This project explores ways to facilitate the responsible clinical translation of cell therapies for the benefit of children, by addressing knowledge gaps and developing resources for researchers, clinicians, families, the committees that approve research proposal, policymakers, and regulators. |
01/01/1970 |
01/01/1970 |
| 2022 |
Jonathan Kimmelman (C) |
Université McGill |
Subventions du programme Applications et Société |
Ravitsky |
Cochercheur |
Vardit Ravitsky, Jonathan Kimmelman, Ma’n Zawati |
70 525 |
Responsible Pathways for Pediatric Cell Therapies |
Multiples maladies |
Cell therapy; clinical trials; first-in-human trials; ethics; law; children’s rights; minors |
Cell therapies hold much promise for the treatment and prevention of disease. Minors are frequently the focus of such interventions, meant to prevent or investigate the expression of early onset diseases. But their inclusion as research participants in clinical trials requires unique ethical and legal protections. This project explores ways to facilitate the responsible clinical translation of cell therapies for the benefit of children, by addressing knowledge gaps and developing resources for researchers, clinicians, families, the committees that approve research proposal, policymakers, and regulators. |
01/01/1970 |
01/01/1970 |
| 2022 |
Ma’n Zawati (C) |
Université McGill |
Subventions du programme Applications et Société |
Ravitsky |
Cochercheur |
Vardit Ravitsky, Jonathan Kimmelman, Ma’n Zawati |
93 060 |
Responsible Pathways for Pediatric Cell Therapies |
Multiples maladies |
Cell therapy; clinical trials; first-in-human trials; ethics; law; children’s rights; minors |
Cell therapies hold much promise for the treatment and prevention of disease. Minors are frequently the focus of such interventions, meant to prevent or investigate the expression of early onset diseases. But their inclusion as research participants in clinical trials requires unique ethical and legal protections. This project explores ways to facilitate the responsible clinical translation of cell therapies for the benefit of children, by addressing knowledge gaps and developing resources for researchers, clinicians, families, the committees that approve research proposal, policymakers, and regulators. |
01/01/1970 |
01/01/1970 |
| 2022 |
Amy Zarzeczny (P) |
University of Regina |
Subventions du programme Applications et Société |
Zarzeczny |
Chercheur principal |
Amy Zarzeczny, Timothy Caulfield, Ubaka Ogbogu |
250 465 |
Law, Public Policy and Social License for Next-Generation Regenerative Medicine |
QEJS, questions éthiques, juridiques et sociales |
Regenerative medicine, law, policy, regulation, governance, public perception, social license |
Regenerative medicine (RM) is an exciting field of research that explores how we can heal or replace damaged or diseased cells, tissues and organs. RM is expected to produce better treatment options for people suffering from conditions like heart disease, muscle and tendon injuries, cornea damage, and skin wounds, among others. Developing successful new therapies requires strong science as well as public trust and support, which is sometimes called a social license. It also requires appropriate regulation and oversight to ensure treatments are safe and effective, and to prevent premature and unethical uses. We will study important areas of RM’s social license including the regulation of new treatments and the conditions under which they can be provided to patients, as well as what kind of misinformation about RM is being circulated in news, social media, and other contexts. Our goal is to support successful clinical translation of RM in Canada by informing ethical and globally relevant governance strategies that provide appropriate oversight and earn public trust. We have a strong interdisciplinary and international team. We will build capacity for leadership in ethical, legal, social and policy issues research in RM with an emphasis on equity, diversity and inclusion in our trainee recruitment and professional development. We will use accessible and high-impact approaches to share our findings with government, policymakers, practitioners, researchers and the public. |
01/01/1970 |
01/01/1970 |
| 2022 |
Timothy Caulfield (C) |
University of Alberta |
Subventions du programme Applications et Société |
Zarzeczny |
Cochercheur |
Amy Zarzeczny, Timothy Caulfield, Ubaka Ogbogu |
265 830 |
Law, Public Policy and Social License for Next-Generation Regenerative Medicine |
QEJS, questions éthiques, juridiques et sociales |
Regenerative medicine, law, policy, regulation, governance, public perception, social license |
Regenerative medicine (RM) is an exciting field of research that explores how we can heal or replace damaged or diseased cells, tissues and organs. RM is expected to produce better treatment options for people suffering from conditions like heart disease, muscle and tendon injuries, cornea damage, and skin wounds, among others. Developing successful new therapies requires strong science as well as public trust and support, which is sometimes called a social license. It also requires appropriate regulation and oversight to ensure treatments are safe and effective, and to prevent premature and unethical uses. We will study important areas of RM’s social license including the regulation of new treatments and the conditions under which they can be provided to patients, as well as what kind of misinformation about RM is being circulated in news, social media, and other contexts. Our goal is to support successful clinical translation of RM in Canada by informing ethical and globally relevant governance strategies that provide appropriate oversight and earn public trust. We have a strong interdisciplinary and international team. We will build capacity for leadership in ethical, legal, social and policy issues research in RM with an emphasis on equity, diversity and inclusion in our trainee recruitment and professional development. We will use accessible and high-impact approaches to share our findings with government, policymakers, practitioners, researchers and the public. |
01/01/1970 |
01/01/1970 |
| 2022 |
Ubaka Ogbogu (C) |
University of Alberta |
Subventions du programme Applications et Société |
Zarzeczny |
Cochercheur |
Amy Zarzeczny, Timothy Caulfield, Ubaka Ogbogu |
188 690 |
Law, Public Policy and Social License for Next-Generation Regenerative Medicine |
QEJS, questions éthiques, juridiques et sociales |
Regenerative medicine, law, policy, regulation, governance, public perception, social license |
Regenerative medicine (RM) is an exciting field of research that explores how we can heal or replace damaged or diseased cells, tissues and organs. RM is expected to produce better treatment options for people suffering from conditions like heart disease, muscle and tendon injuries, cornea damage, and skin wounds, among others. Developing successful new therapies requires strong science as well as public trust and support, which is sometimes called a social license. It also requires appropriate regulation and oversight to ensure treatments are safe and effective, and to prevent premature and unethical uses. We will study important areas of RM’s social license including the regulation of new treatments and the conditions under which they can be provided to patients, as well as what kind of misinformation about RM is being circulated in news, social media, and other contexts. Our goal is to support successful clinical translation of RM in Canada by informing ethical and globally relevant governance strategies that provide appropriate oversight and earn public trust. We have a strong interdisciplinary and international team. We will build capacity for leadership in ethical, legal, social and policy issues research in RM with an emphasis on equity, diversity and inclusion in our trainee recruitment and professional development. We will use accessible and high-impact approaches to share our findings with government, policymakers, practitioners, researchers and the public. |
01/01/1970 |
01/01/1970 |
| 2022 |
Manoj Lalu (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions du programme Applications et Société |
Lalu |
Chercheur principal |
Manoj Lalu |
300 000 |
Engaging patients in laboratory-based cell therapy research: Co-production and field testing of a framework |
QEJS, questions éthiques, juridiques et sociales |
patient engagement, patient and public involvement, patient oriented research |
Patient engagement in research means patients are partners on a research team to provide input on various matters. While this practice is becoming more common in clinical (human) research, it is less often used in lab (cell/animal) research. We believe engaging patients in SCN funded research is important. We want to develop guidance for researchers and patient partners in this area. Our team previously identified all lab studies that included patient engagement and interviewed scientists and patients involved. Although few studies were identified, we found that patients can be involved in various aspects of lab research, including identifying priorities and presenting findings. Patient engagement improved researchers’ understanding of the real-life implications of their work, while patient partners gained new insights into biomedical research. _x000D_
_x000D_
The main aim of our project is to identify how SCN funded researchers and patient partners can work together on lab studies and to identify methods that will improve this process. This guidance will be co-developed alongside a team of patients and cell therapy/regenerative medicine researchers. We will also invite SCN lab groups (including trainees) and patients to test the framework, and then participate in focus groups to ask for their feedback. The developed guidance will outline promising practices for patient engagement in preclinical cell therapy research and allow more partnerships to be formed. |
01/01/1970 |
01/01/1970 |
| 2023 |
Bruce Verchere (P) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Chercheur principal |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
188 000 |
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes |
Diabète |
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR. |
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes. |
01/01/1970 |
01/01/1970 |
| 2023 |
Francis Lynn (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
188 000 |
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes |
Diabète |
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR. |
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes. |
01/01/1970 |
01/01/1970 |
| 2023 |
Megan Levings (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
188 000 |
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes |
Diabète |
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR. |
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes. |
01/01/1970 |
01/01/1970 |
| 2023 |
Timothy Kieffer (C) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Verchere |
Cochercheur |
Bruce Verchere, Francis Lynn, Megan Levings, Timothy Kieffer |
36 000 |
Genetic engineering of hESC-derived insulin-producing cells to improve graft outcomes in type 1 diabetes |
Diabète |
human embryonic stem cells, beta cells, type 1 diabetes, insulin, transplantation, islet amyloid, chemokine, allograft rejection, CAR T cells, CRISPR. |
Type 1 diabetes is a devastating disease in which insulin-producing cells in the pancreas are destroyed by the immune system, leaving persons dependent on insulin injections for life, and at risk for serious complications due to fluctuating blood sugars. Replacement of the lost insulin-producing cells by transplantation is a promising therapy that has potential to allow persons with type 1 diabetes to live free of insulin and without worry of the complications of the disease, but there are not enough organ donors to provide cells for all people living with type 1 diabetes, and in most persons who have received insulin-producing cell transplants from organ donors, the transplants fail and they must return to taking insulin injections. Recent advances now enable scientists to make human insulin-producing cells in the lab from stem cells. These cells have great promise as a potentially limitless source of cells for transplantation in persons with type 1 diabetes. In addition, new gene editing technologies have created the potential to make better insulin-producing cells from stem cells. We have assembled a team of scientists with expertise in stem cells, diabetes, and transplantation, and propose to work together to engineer insulin-producing cells that will work better and last longer following transplantation. The goal is to create a new cell therapy that could enable thousands to live free of the tremendous burden of diabetes. |
01/01/1970 |
01/01/1970 |
| 2023 |
Véronique Moulin (P) |
Université Laval |
Subventions de soutien à l’accélération de la transposition clinique |
Moulin |
Chercheur principal |
Véronique Moulin, Ma'n Zawati, Chanel Beaudoin-Cloutier, Lucie Germain |
532 000 |
Allogeneic dermis to accelerate the production of a tissue-engineered skin substitute to treat Canadian burn patients |
Brûlures et cicatrisation |
tissue engineering, skin, burn, allogenic dermis, acute wound, clinical trial, stem cells |
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients. |
01/01/1970 |
01/01/1970 |
| 2023 |
Ma'n Zawati (C) |
McGill University |
Subventions de soutien à l’accélération de la transposition clinique |
Moulin |
Cochercheur |
Véronique Moulin, Ma'n Zawati, Chanel Beaudoin-Cloutier, Lucie Germain |
20 000 |
Allogeneic dermis to accelerate the production of a tissue-engineered skin substitute to treat Canadian burn patients |
Brûlures et cicatrisation |
tissue engineering, skin, burn, allogenic dermis, acute wound, clinical trial, stem cells |
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients. |
01/01/1970 |
01/01/1970 |
| 2023 |
Chanel Beaudoin-Cloutier (C) |
Université Laval |
Subventions de soutien à l’accélération de la transposition clinique |
Moulin |
Cochercheur |
Véronique Moulin, Ma'n Zawati, Chanel Beaudoin-Cloutier, Lucie Germain |
16 000 |
Allogeneic dermis to accelerate the production of a tissue-engineered skin substitute to treat Canadian burn patients |
Brûlures et cicatrisation |
tissue engineering, skin, burn, allogenic dermis, acute wound, clinical trial, stem cells |
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients. |
01/01/1970 |
01/01/1970 |
| 2023 |
Lucie Germain (C) |
Université Laval |
Subventions de soutien à l’accélération de la transposition clinique |
Moulin |
Cochercheur |
Véronique Moulin, Ma'n Zawati, Chanel Beaudoin-Cloutier, Lucie Germain |
32 000 |
Allogeneic dermis to accelerate the production of a tissue-engineered skin substitute to treat Canadian burn patients |
Brûlures et cicatrisation |
tissue engineering, skin, burn, allogenic dermis, acute wound, clinical trial, stem cells |
The treatment of burn wounds is based on skin autografts. When looking to cover more than half of the body surface area, treatment with autografts becomes strategic as the extent of the burns reduces available healthy donor sites to harvest autografts. With the tissue engineering methods developed in our lab, Self-Assembled Skin Substitutes (SASS) can be produced from a small piece of patient’s skin and permanently cover all wounds. However, the main drawback of this new technology is the production time: from the time the biopsy is done to the first graft, it takes about 8 weeks. For burn patients, this delay is too long and they urge us to shorten it. Two cell types are needed to produce SASS: fibroblasts and keratinocytes. To shorten SASS production delay, our strategy is to use fibroblasts isolated from another donor because fibroblasts do not cause graft rejection. Keratinocytes, that cause graft rejection, will be those of the patient as usual. Before testing this new SASS on patients, we need to prepare a biobank with fibroblasts that meet Health Canada’s sterility and safety requirements as well as our own parameters. _x000D_
Our team is composed of four internationally renowned researchers. We are the only Canadian team dedicated to the reconstruction of tissues. The production of a fibroblast biobank is the first step to produce the new SASS which will eventually improve and reduce hospital length of stay of burn patients. |
01/01/1970 |
01/01/1970 |
| 2023 |
Juan Carlos Zúñiga-Pflücker (P) |
Sunnybrook Research Institute |
Subventions de soutien à l’accélération de la transposition clinique |
Zúñiga-Pflücker |
Chercheur principal |
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson |
407 375 |
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTIMM) |
Immunothérapie; cancer |
Immunodeficiency, Blood stem cells, Bone marrow translansplant, Thymic reconstitution, T cells, Cancer treatment |
Current treatments some blood cancers involve the use chemotherapy and/or radiation treatment followed by hematopoietic stem cell transplant (HSCT). T cells, which are key components of the immune system, remain absent or at low levels for months to years after HSCT. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects, lengthy treatment with antibiotics and antivirals, and in some cases infusion of donor T-cells are required. However, donor T cells may also attack healthy tissues and cause graft-versus-host disease that may lead to organ failure and death._x000D_
To provide patients with a much-needed safe T cell boost, we have developed a novel way of generating progenitor T (proT) cells from donor blood stem cells in a clinically compatible culture. This method will help speed replenishment of T-cells post-HSCT, as infused proT cells will seed the thymus of patients, where they develop into mature T cells. ProT cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Studies in animal models have demonstrated that this is an effective and potentially curative treatment in both young and aged. Hence, proT cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse. |
01/01/1970 |
01/01/1970 |
| 2023 |
Donna Wall (C) |
Hospital for Sick Children |
Subventions de soutien à l’accélération de la transposition clinique |
Zúñiga-Pflücker |
Cochercheur |
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson |
101 500 |
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTIMM) |
Immunothérapie; cancer |
Immunodeficiency, Blood stem cells, Bone marrow translansplant, Thymic reconstitution, T cells, Cancer treatment |
Current treatments some blood cancers involve the use chemotherapy and/or radiation treatment followed by hematopoietic stem cell transplant (HSCT). T cells, which are key components of the immune system, remain absent or at low levels for months to years after HSCT. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects, lengthy treatment with antibiotics and antivirals, and in some cases infusion of donor T-cells are required. However, donor T cells may also attack healthy tissues and cause graft-versus-host disease that may lead to organ failure and death._x000D_
To provide patients with a much-needed safe T cell boost, we have developed a novel way of generating progenitor T (proT) cells from donor blood stem cells in a clinically compatible culture. This method will help speed replenishment of T-cells post-HSCT, as infused proT cells will seed the thymus of patients, where they develop into mature T cells. ProT cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Studies in animal models have demonstrated that this is an effective and potentially curative treatment in both young and aged. Hence, proT cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse. |
01/01/1970 |
01/01/1970 |
| 2023 |
Jonas Mattsson (C) |
University Health Network |
Subventions de soutien à l’accélération de la transposition clinique |
Zúñiga-Pflücker |
Cochercheur |
Juan Carlos Zúñiga-Pflücker, Donna Wall, Jonas Mattsson |
91 000 |
Production of progenitor T cells for immune-reconstitution and targeted immunotherapies (ProTIMM) |
Immunothérapie; cancer |
Immunodeficiency, Blood stem cells, Bone marrow translansplant, Thymic reconstitution, T cells, Cancer treatment |
Current treatments some blood cancers involve the use chemotherapy and/or radiation treatment followed by hematopoietic stem cell transplant (HSCT). T cells, which are key components of the immune system, remain absent or at low levels for months to years after HSCT. This increases susceptibility to cancer relapse and opportunistic infections. To help control these adverse effects, lengthy treatment with antibiotics and antivirals, and in some cases infusion of donor T-cells are required. However, donor T cells may also attack healthy tissues and cause graft-versus-host disease that may lead to organ failure and death._x000D_
To provide patients with a much-needed safe T cell boost, we have developed a novel way of generating progenitor T (proT) cells from donor blood stem cells in a clinically compatible culture. This method will help speed replenishment of T-cells post-HSCT, as infused proT cells will seed the thymus of patients, where they develop into mature T cells. ProT cells also have the effect of repairing thymus after its injury due to chemo/radiation treatment. Importantly, apart from conferring immunity, the emerging T-cell would also be tolerant to host and would not cause graft-versus-host disease. Studies in animal models have demonstrated that this is an effective and potentially curative treatment in both young and aged. Hence, proT cells would likely improve the quality of life of HSCT patients by decreasing their susceptibility to deadly infections and relapse. |
01/01/1970 |
01/01/1970 |
| 2023 |
Bernard Thébaud (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien à l’accélération de la transposition clinique |
Thébaud |
Chercheur principal |
Bernard Thébaud, Dean Fergusson, Justin Presseau |
532 400 |
AAVenger-B: Adeno-Associated Virus Engineered Gene Epithelial progenitor cell Regeneration for surfactant proteinB deficiency |
Maladie pulmonaire, maladies pulmonaires, maladie des poumons, maladies des poumons |
Lung regeneration, Lung epithelial stem/progenitor cell, Lung disease, Gene therapy, Adeno-associated virus (AAV), Clinical trial, Newborn |
Lung diseases due to a defect in a single gene lead to failure to breath at birth and early death, or lung scarring (fibrosis) in later life. There are no targeted therapies. Surfactant proteins A, B, C, and D as well as the ATP-binding cassette sub-family A member 3 (ABCA3) are critical to keep the air sacs in the lung open for efficient oxygen intake. Surfactant protein B (SPB) deficiency is the most severe form, leading to respiratory failure at birth._x000D_
Treatment with exogenous surfactant provides only transient improvement and without lung transplantation, SPB is lethal within the first year of life. SPB is amenable to targeted airway delivery of a gene therapy to insert a normal SPB gene. We have engineered an innovative viral vector (AAV6.2FF) to treat SPB. AAV6.2FF selectively transduces alveolar type II cells (AT2) cells that produce surfactant and leads to rapid expression of SPB. In a mouse model lacking SPB, AAV6.2FF dramatically improves lung function and achieves unprecedented survival. These results demonstrate the promise of AAV6.2FF to treat, and potentially cure, SPB. This has led to a patent and a spin-off company (Inspire Biotherapeutics) with the goal of manufacturing new regenerative medicine products to be used in patients. We will develop AAV6.2FF gene therapy as a platform for the treatment of a variety of genetic lung diseases. |
01/01/1970 |
01/01/1970 |
| 2023 |
Dean Fergusson (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien à l’accélération de la transposition clinique |
Thébaud |
Cochercheur |
Bernard Thébaud, Dean Fergusson, Justin Presseau |
37 000 |
AAVenger-B: Adeno-Associated Virus Engineered Gene Epithelial progenitor cell Regeneration for surfactant proteinB deficiency |
Maladie pulmonaire, maladies pulmonaires, maladie des poumons, maladies des poumons |
Lung regeneration, Lung epithelial stem/progenitor cell, Lung disease, Gene therapy, Adeno-associated virus (AAV), Clinical trial, Newborn |
Lung diseases due to a defect in a single gene lead to failure to breath at birth and early death, or lung scarring (fibrosis) in later life. There are no targeted therapies. Surfactant proteins A, B, C, and D as well as the ATP-binding cassette sub-family A member 3 (ABCA3) are critical to keep the air sacs in the lung open for efficient oxygen intake. Surfactant protein B (SPB) deficiency is the most severe form, leading to respiratory failure at birth._x000D_
Treatment with exogenous surfactant provides only transient improvement and without lung transplantation, SPB is lethal within the first year of life. SPB is amenable to targeted airway delivery of a gene therapy to insert a normal SPB gene. We have engineered an innovative viral vector (AAV6.2FF) to treat SPB. AAV6.2FF selectively transduces alveolar type II cells (AT2) cells that produce surfactant and leads to rapid expression of SPB. In a mouse model lacking SPB, AAV6.2FF dramatically improves lung function and achieves unprecedented survival. These results demonstrate the promise of AAV6.2FF to treat, and potentially cure, SPB. This has led to a patent and a spin-off company (Inspire Biotherapeutics) with the goal of manufacturing new regenerative medicine products to be used in patients. We will develop AAV6.2FF gene therapy as a platform for the treatment of a variety of genetic lung diseases. |
01/01/1970 |
01/01/1970 |
| 2023 |
Justin Presseau (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions de soutien à l’accélération de la transposition clinique |
Thébaud |
Cochercheur |
Bernard Thébaud, Dean Fergusson, Justin Presseau |
30 400 |
AAVenger-B: Adeno-Associated Virus Engineered Gene Epithelial progenitor cell Regeneration for surfactant proteinB deficiency |
Maladie pulmonaire, maladies pulmonaires, maladie des poumons, maladies des poumons |
Lung regeneration, Lung epithelial stem/progenitor cell, Lung disease, Gene therapy, Adeno-associated virus (AAV), Clinical trial, Newborn |
Lung diseases due to a defect in a single gene lead to failure to breath at birth and early death, or lung scarring (fibrosis) in later life. There are no targeted therapies. Surfactant proteins A, B, C, and D as well as the ATP-binding cassette sub-family A member 3 (ABCA3) are critical to keep the air sacs in the lung open for efficient oxygen intake. Surfactant protein B (SPB) deficiency is the most severe form, leading to respiratory failure at birth._x000D_
Treatment with exogenous surfactant provides only transient improvement and without lung transplantation, SPB is lethal within the first year of life. SPB is amenable to targeted airway delivery of a gene therapy to insert a normal SPB gene. We have engineered an innovative viral vector (AAV6.2FF) to treat SPB. AAV6.2FF selectively transduces alveolar type II cells (AT2) cells that produce surfactant and leads to rapid expression of SPB. In a mouse model lacking SPB, AAV6.2FF dramatically improves lung function and achieves unprecedented survival. These results demonstrate the promise of AAV6.2FF to treat, and potentially cure, SPB. This has led to a patent and a spin-off company (Inspire Biotherapeutics) with the goal of manufacturing new regenerative medicine products to be used in patients. We will develop AAV6.2FF gene therapy as a platform for the treatment of a variety of genetic lung diseases. |
01/01/1970 |
01/01/1970 |
| 2023 |
Peter Zandstra (P) |
University of British Columbia |
Subventions de soutien à l’accélération de la transposition clinique |
Zandstra |
Chercheur principal |
Peter Zandstra, Yale Michaels |
218 034 |
PSC-derived immune cells as an advanced delivery vehicle for protein therapeutics |
Produits thérapeutiques à base de protéines |
Stem cells, B cells, inflammation, synthetic biology, developmental immunology |
Our aim is to address the challenge of treating chronic inflammatory disease, a group of conditions that impact more than 6 million Canadians. Protein-based medicines called biologics can effectively treat inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis. Unfortunately, for these biologics to be effective, they must be dosed by injections every few weeks. These injections are painful and cause the medicine to travel all over the body leading to side-effects. Furthermore, frequent treatments with biologics are expensive- they can cost more than $70,000 per year per patient. Our goal is to address these limitations by using living cells to make and release biologics from within the body. We are using a type of immune cell called a B cell for this job because B cells can survive in the body for decades and can make and release large quantities of protein. We plan to genetically modify B cells so that they will only make and release their therapy when they sense inflammation within the body. This will help avoid unwanted side effects. Rather than getting B cells from human donors, which is very expensive, we will make our B cell product from human stem cells which can be grown extensively outside of the body. This will allow us to make an affordable medicine that will be accessible to patients. This project will help our partner organisation, Apiary Therapeutics, grow as a company and continue to hire highly skilled Canadians. |
01/01/1970 |
01/01/1970 |
| 2023 |
Yale Michaels (C) |
CancerCare Manitoba |
Subventions de soutien à l’accélération de la transposition clinique |
Zandstra |
Cochercheur |
Peter Zandstra, Yale Michaels |
181 966 |
PSC-derived immune cells as an advanced delivery vehicle for protein therapeutics |
Produits thérapeutiques à base de protéines |
Stem cells, B cells, inflammation, synthetic biology, developmental immunology |
Our aim is to address the challenge of treating chronic inflammatory disease, a group of conditions that impact more than 6 million Canadians. Protein-based medicines called biologics can effectively treat inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis. Unfortunately, for these biologics to be effective, they must be dosed by injections every few weeks. These injections are painful and cause the medicine to travel all over the body leading to side-effects. Furthermore, frequent treatments with biologics are expensive- they can cost more than $70,000 per year per patient. Our goal is to address these limitations by using living cells to make and release biologics from within the body. We are using a type of immune cell called a B cell for this job because B cells can survive in the body for decades and can make and release large quantities of protein. We plan to genetically modify B cells so that they will only make and release their therapy when they sense inflammation within the body. This will help avoid unwanted side effects. Rather than getting B cells from human donors, which is very expensive, we will make our B cell product from human stem cells which can be grown extensively outside of the body. This will allow us to make an affordable medicine that will be accessible to patients. This project will help our partner organisation, Apiary Therapeutics, grow as a company and continue to hire highly skilled Canadians. |
01/01/1970 |
01/01/1970 |
| 2023 |
Sowmya Viswanathan (P) |
University Health Network |
Subventions de soutien des essais cliniques |
Viswanathan |
Chercheur principal |
Sowmya Viswanathan |
750 000 |
Autologous Bone Marrow Aspirate Concentrate or Lipoaspirate Concentrate for OsteoArthritis: ABLE OA Clinical Trial |
Ostéoarthrite, ostéo-arthrite |
Cellular therapy,bone marrow aspirate,lipoaspirate,mesenchymal stromal cells,paracrine effects, educing inflammation,endogenous chondrocyte repair |
Joint pain and disability affect 1 in 6 Canadians. There is no cure; patients manage their pain with short lasting treatments. In this clinical trial, we are looking to test two types of preparations that are made from the patient’s bone marrow or fat. These preparations have been used to treat painful joints for years. Health Canada decided to require additional proof in well designed and controlled clinical trials before these preparations could be offered routinely to all patients. The clinical trial we are proposing is well designed; patients are randomly selected to be part of a treatment arm where they will receive their own bone marrow or fat, or a placebo arm, where they will be injected with salt water. They will not know which arm they are in, nor will the clinicians. This design allows us to isolate the real effect from this “placebo” effect. We expect patients in the treatment arm to have greater pain relief and better ability to perform daily activities. Our trial is not only well designed but also answers basic biology questions about why some patients respond well while others do not. We think this is because some patients have more inflammation in their joints and body. We will match the level of inflammation in patients to whether the patients respond well or not. Altogether, our trial will provide access to Canadian patients to new treatments to manage their joint pain and disability and help answer fundamental questions about how these treatments work. |
01/01/1970 |
01/01/1970 |
| 2023 |
Marc Jeschke (P) |
McMaster University |
Subventions de soutien des essais cliniques |
Jeschke |
Chercheur principal |
Marc Jeschke |
298 000 |
A phase I, single-blind, randomized study of safety of cellularized Integra® using autologous burn-derived MSCs |
Brûlures et cicatrisation |
wound healing, Integra, regeneration, burns, burn-derived mesenchymal stem cells |
The single most important factor that determines survival of a burn patient is wound healing. We recently made a discovery that could revolutionize management of burn patients when we isolated cells identified as burn-derived mesenchymal stem cells (BD-MSCs) from discarded burned skin. We then developed Integra®-SC a skin substitute that was engineered by incorporating BD-MSCs into Integra®, a dermal matrix, and found beneficial results in both small and large animal models. We now propose to conduct a first-in-humans clinical trial at an academic hospital in Ontario. We will use Integra®-SC, developed from a patient’s own surgically removed burned tissue, to place on their excised burn wounds. We believe that Integra®-SC will facilitate and improve wound healing, heal faster, and, in the long-term, result in less scar formation. Burn surgeons can utilize Integra®-SC to avoid surgically removing a patient’s own good uninjured skin to use as a donor. Donor sites also need to heal, are often sources of pain, and can scar. This study will be done in stages followed by interim safety analyses. After safety analyses, we will evaluate any needs or gaps in order to include recruitment of patients with a larger percent total body surface area burn. The clinical applicability of Integra®-SC is promising and could create a new standard for burn patients in Ontario and worldwide, further providing a broader clinical application and impacts patients with traumatic and complex wounds. |
01/01/1970 |
01/01/1970 |
| 2023 |
Lucie Germain (P) |
Université Laval |
Subventions de soutien des essais cliniques |
Germain |
Chercheur principal |
Lucie Germain |
603 600 |
Clinical trial of cultured epithelial corneal autografts for the treatment of Canadians with limbal stem cell deficiency |
Maladie des yeux, maladies des yeux; maladie oculaire |
Epithelium, Stem cells, Autologous graft, Eye/ cornea, Tissue engineering, culture |
Limbal stem cell deficiency (LSCD) is a severe disease caused by damage or decrease of stem cells in an area of the eye called the “corneal limbal region,” following trauma or disease. The LOEX/CHU de Québec-Université Laval, a leader in cell therapies, is performing the first clinical trial in Canada offering a treatment for LSCD using “cultured epithelial corneal autograft (CECA).” The CECA involves taking a small piece of tissue from the healthy eye to grow cells to produce CECA and then grafting it back into the affected eye. The LOEX has been successfully producing CECA since 2012. _x000D_
Our interdisciplinary team brings together experts in tissue-engineering and economic, ethical/legal issues, ophthalmology, pathology, research professionals and also a patient representative. _x000D_
The objective of the present proposal is to continue our multicenter (Quebec, Montreal and Toronto) clinical trial to evaluate the effectiveness and safety of the CECA treatment. We expect to recruit and treat 12 adult patients. The number of patients for the entire clinical study will be 49 adult patients and 5 minor patients._x000D_
Without treatment, LSCD results in severe visual impairments affecting the quality of life of patients and their families. LSCD affects patients' ability to work, drive and conduct daily activities. Therefore, this innovative treatment, if proven successful, could change the lives of Canadian patients affected by this rare disease by improving vision in their affected eye. |
01/01/1970 |
01/01/1970 |
| 2023 |
Michael Fehlings (P) |
University Health Network |
Subventions de soutien aux partenariats biotechnologiques |
Fehlings |
Chercheur principal |
Michael Fehlings |
400 000 |
Translation of cGMP grade oligodenrogenic NPCs (oNPCs) for the treatment of traumatic cervical spinal cord injury |
Lésion de la moelle épinière |
neural stem cells, hiPSC, GMP, spinal cord injury |
Spinal cord injuries (SCIs), frequently the result of falls or road traffic accidents, have devastating long-term physical, social, and financial impacts on patients and their families. Currently, there are no effective therapies available for the treatment of SCI. Damage to the spinal cord results in the loss of I) cells critical for sending signals from the brain to the rest of the body and ii) myelin, a substance that insulates nerves to ensure signals can travel efficiently. Without these signals, a person’s ability to perform everyday activities such as walking, grasping, holding and controlling bowel / bladder function is compromised, which results in debilitating impairments such as para/quadriplegia and death. Stem cells show exciting promise for treating SCI patients due to their ability to replace any cell type within the human body. This application focuses on a strategy to repair the injured spinal cord using human stem cells that have been generated to repair the myelin damage frequently observed following a SCI. This work is the culmination of over 16 years of research into the fields of SCI and stem cells by my lab, which has now partnered with Inteligex; the only Canadian-based regenerative medicine company working on a stem cell-based therapy for SCI. The aim of this proposal is to develop this stem cell-based therapeutic approach as a viable treatment option for individuals who sustain a SCI. |
01/01/1970 |
01/01/1970 |
| 2023 |
C. Florian Bentzinger (P) |
Université de Sherbrooke |
Subventions de soutien aux partenariats biotechnologiques |
Bentzinger |
Chercheur principal |
C. Florian Bentzinger |
398 600 |
Mobilizing endogenous repair in muscular dystrophy |
Maladie musculaire, maladies musculaires |
muscle stem cells, satellite cells, muscular dystrophy, endogenous repair, extracellular matrix, dystrophin glycoprotein complex |
Muscular dystrophies (MDs) are a group of rare muscle wasting diseases that often affect kids. To date, no effective treatment options are available for MD. The causes of different forms of MD are highly diverse, which makes it difficult to develop treatments that can be used for all patients. We discovered that in several different mouse models of MD, the ability of muscle to repair itself is strongly reduced. The Canadian Biotechnology company Satellos has identified a drug that is able to correct muscle repair defects by stimulation of tissue-resident stem cells. Here, we propose to partner with Satellos to study the effects of this unique treatment approach in mouse models of two particularly severe forms of MD, try to better understand the molecular changes induced by the drug, and test if it can be combined with other regenerative therapies. The study we propose will lay the ground-work for a much-needed novel and highly efficient drug that can potentially be used to treat many different forms of MD. A stem cell targeted therapeutic agent boosting the innate repair capacity of skeletal muscle represents an unprecedented and disruptive discovery that would pioneer a novel class of therapeutics with the potential to have a dramatic impact on the quality of life of patients affected by these devastating diseases. |
01/01/1970 |
01/01/1970 |
| 2023 |
Massimiliano Paganelli (P) |
Centre Hospitalier Universitaire Sainte-Justine |
Subventions de soutien aux partenariats biotechnologiques |
Paganelli |
Chercheur principal |
Massimiliano Paganelli, Christopher Rose |
320 000 |
iPSC-derived Encapsulated Liver Tissue: extending the indication to acute-on-chronic liver failure |
Maladies du foie, maladie du foie, maladie hépatique |
liver failure, allogeneic cell therapy, tissue engineering, iPSC, liver failure |
Acute-on-chronic liver failure (ACLF) consists in an acute decompensation of the vital functions of the liver and other organs happening in people suffering from chronic liver disease. No treatment exists for ACLF other than liver transplantation, which is only possible for only a minority of patients. Over the last 5 years, with the support of the Stem Cell Network, we have developed an innovative treatment consisting in an implantable, stem cell-derived liver tissue that is effective in treating acute forms of liver failure, at least in experimental conditions. With this project we aim at assessing whether this treatment, that we call Encapsulated Liver Tissue (ELT), is also effective in treating ACLF. We will test the behavior of the ELT in the peculiar conditions characterizing ACLF and measure its efficacy in treating ACLF-related complications and improving survival of relevant animal models. If successful, this project will allow expanding the indications of the ELT to ACLF, which in turn will allow us and our partner, the regenerative medicine company Morphocell Technologies, to reach more patients in need. |
01/01/1970 |
01/01/1970 |
| 2023 |
Christopher Rose (C) |
Centre Hospitalier de l'Université de Montréal |
Subventions de soutien aux partenariats biotechnologiques |
Paganelli |
Cochercheur |
Massimiliano Paganelli, Christopher Rose |
80 000 |
iPSC-derived Encapsulated Liver Tissue: extending the indication to acute-on-chronic liver failure |
Maladies du foie, maladie du foie, maladie hépatique |
liver failure, allogeneic cell therapy, tissue engineering, iPSC, liver failure |
Acute-on-chronic liver failure (ACLF) consists in an acute decompensation of the vital functions of the liver and other organs happening in people suffering from chronic liver disease. No treatment exists for ACLF other than liver transplantation, which is only possible for only a minority of patients. Over the last 5 years, with the support of the Stem Cell Network, we have developed an innovative treatment consisting in an implantable, stem cell-derived liver tissue that is effective in treating acute forms of liver failure, at least in experimental conditions. With this project we aim at assessing whether this treatment, that we call Encapsulated Liver Tissue (ELT), is also effective in treating ACLF. We will test the behavior of the ELT in the peculiar conditions characterizing ACLF and measure its efficacy in treating ACLF-related complications and improving survival of relevant animal models. If successful, this project will allow expanding the indications of the ELT to ACLF, which in turn will allow us and our partner, the regenerative medicine company Morphocell Technologies, to reach more patients in need. |
01/01/1970 |
01/01/1970 |
| 2023 |
Fabio Rossi (P) |
University of British Columbia |
Subventions de soutien aux partenariats biotechnologiques |
Rossi |
Chercheur principal |
Fabio Rossi, Bettina Willie, Frank Rauch |
194 121 |
Bone targeted EP4 agonists as therapeutics for muscular dystrophy |
Maladie musculaire, maladies musculaires |
Duchenne Muscular Dystrophy, bone regeneration, muscle regeneration, PGE2, |
Patients suffering from Duchenne muscular dystrophy lose muscle mass and function, and eventually bone mass. This leads to a dramatic decrease in their quality of life, as they are susceptible to vertebral fractures that are extremely painful. A specific molecule, prostaglandin E2 (PGE2), acts by strengthening both bones and muscle by enhancing their regeneration. However, it cannot be used in humans as it causes unpleasant and dangerous digestive system side effects at the level of the intestinal mucosa. Our partner Mesentech has developed a new compound that releases a PGE2 analog only at the bone surface. Preliminary results indicate that this compound is extremely effective in rebuilding bone, and surprisingly it also affects skeletal muscle, significantly increasing its mass. Here, we propose to optimize the treatment regime and assess whether this compound can lead to improved tissue function (more break-resistant bone, stronger muscle) as well as explore the underlying biological mechanisms of drug action. |
01/01/1970 |
01/01/1970 |
| 2023 |
Bettina Willie (C) |
Université McGill |
Subventions de soutien aux partenariats biotechnologiques |
Rossi |
Cochercheur |
Fabio Rossi, Bettina Willie, Frank Rauch |
108 740 |
Bone targeted EP4 agonists as therapeutics for muscular dystrophy |
Maladie musculaire, maladies musculaires |
Duchenne Muscular Dystrophy, bone regeneration, muscle regeneration, PGE2, |
Patients suffering from Duchenne muscular dystrophy lose muscle mass and function, and eventually bone mass. This leads to a dramatic decrease in their quality of life, as they are susceptible to vertebral fractures that are extremely painful. A specific molecule, prostaglandin E2 (PGE2), acts by strengthening both bones and muscle by enhancing their regeneration. However, it cannot be used in humans as it causes unpleasant and dangerous digestive system side effects at the level of the intestinal mucosa. Our partner Mesentech has developed a new compound that releases a PGE2 analog only at the bone surface. Preliminary results indicate that this compound is extremely effective in rebuilding bone, and surprisingly it also affects skeletal muscle, significantly increasing its mass. Here, we propose to optimize the treatment regime and assess whether this compound can lead to improved tissue function (more break-resistant bone, stronger muscle) as well as explore the underlying biological mechanisms of drug action. |
01/01/1970 |
01/01/1970 |
| 2023 |
Frank Rauch (C) |
Université McGill |
Subventions de soutien aux partenariats biotechnologiques |
Rossi |
Cochercheur |
Fabio Rossi, Bettina Willie, Frank Rauch |
96 960 |
Bone targeted EP4 agonists as therapeutics for muscular dystrophy |
Maladie musculaire, maladies musculaires |
Duchenne Muscular Dystrophy, bone regeneration, muscle regeneration, PGE2, |
Patients suffering from Duchenne muscular dystrophy lose muscle mass and function, and eventually bone mass. This leads to a dramatic decrease in their quality of life, as they are susceptible to vertebral fractures that are extremely painful. A specific molecule, prostaglandin E2 (PGE2), acts by strengthening both bones and muscle by enhancing their regeneration. However, it cannot be used in humans as it causes unpleasant and dangerous digestive system side effects at the level of the intestinal mucosa. Our partner Mesentech has developed a new compound that releases a PGE2 analog only at the bone surface. Preliminary results indicate that this compound is extremely effective in rebuilding bone, and surprisingly it also affects skeletal muscle, significantly increasing its mass. Here, we propose to optimize the treatment regime and assess whether this compound can lead to improved tissue function (more break-resistant bone, stronger muscle) as well as explore the underlying biological mechanisms of drug action. |
01/01/1970 |
01/01/1970 |
| 2023 |
Jason Guertin (P) |
Université Laval |
Subventions aux projets à fort impact : filière des QEJS |
Guertin |
Chercheur principal |
Jason Guertin |
200 000 |
Supporting the use of early economic evaluations within the regenerative medicine field |
Économie de la santé |
Economic evaluation, Cost data, Health technology assessment, Regenerative medicine, Knowledge translation, Reimbursement, Economic modelling |
Though health technologies must be effective before they are made widely available to Canadians, healthcare systems often require they be cost-effective as well. Unfortunately, expertise regarding the economic components of regenerative medicine technologies is scarce._x000D_
_x000D_
This proposal combines a series of real-world projects aimed at examining the cost of a specific regenerative medicine technology, the self-assembled skin substitute (SASS), which is currently being used to treat severely burned patients. Once complete, we will use the experience gained in this first series of projects to design a series of knowledge mobilization tools tailored to fundamental and clinical researchers so as to help them plan their own future economic studies._x000D_
_x000D_
By doing so, we will not only help bring an innovative technology, SASS, to Canadians but also help other Canadian researchers plan economic studies that will be required for the technologies they are creating. |
01/01/1970 |
01/01/1970 |
| 2023 |
Manoj Lalu (P) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions aux projets à fort impact : filière des QEJS |
Lalu |
Chercheur principal |
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz |
101 142 |
Developing guidance to translate promising cell therapies to early phase clinical trials |
Participation des patients à la recherche, engagement des patients |
Preclinical, Experimental Design, Confirmatory Cell Therapy Trial, Bench-to-Bedside Translation, Systematic/Scoping Review, Interview Study, Delphi |
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials. |
01/01/1970 |
01/01/1970 |
| 2023 |
Jonathan Kimmelman (C) |
McGill University |
Subventions aux projets à fort impact : filière des QEJS |
Lalu |
Cochercheur |
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz |
15 000 |
Developing guidance to translate promising cell therapies to early phase clinical trials |
Participation des patients à la recherche, engagement des patients |
Preclinical, Experimental Design, Confirmatory Cell Therapy Trial, Bench-to-Bedside Translation, Systematic/Scoping Review, Interview Study, Delphi |
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials. |
01/01/1970 |
01/01/1970 |
| 2023 |
Dean Fergusson (C) |
L'Institut de recherche de l'Hôpital d'Ottawa |
Subventions aux projets à fort impact : filière des QEJS |
Lalu |
Cochercheur |
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz |
53 859 |
Developing guidance to translate promising cell therapies to early phase clinical trials |
Participation des patients à la recherche, engagement des patients |
Preclinical, Experimental Design, Confirmatory Cell Therapy Trial, Bench-to-Bedside Translation, Systematic/Scoping Review, Interview Study, Delphi |
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials. |
01/01/1970 |
01/01/1970 |
| 2023 |
Agnes Grudniewicz (C) |
Université d’Ottawa |
Subventions aux projets à fort impact : filière des QEJS |
Lalu |
Cochercheur |
Manoj Lalu, Jonathan Kimmelman, Dean Fergusson, Agnes Grudniewicz |
30 000 |
Developing guidance to translate promising cell therapies to early phase clinical trials |
Participation des patients à la recherche, engagement des patients |
Preclinical, Experimental Design, Confirmatory Cell Therapy Trial, Bench-to-Bedside Translation, Systematic/Scoping Review, Interview Study, Delphi |
Testing new treatments in humans is slow (up to 10-20 years) and expensive (hundreds of millions of dollars). Testing new treatments in animals can be a good way to save time, money, and try many types of treatments, but very few treatments that seem to work in animals, end up working well in humans. This is partly because there is no agreement on how we should do animal testing, or judge if a treatment has a good chance of working in humans. Reaching an agreement on the most important details might help us improve the way we test new treatments and how we choose promising cell therapies to enter clinical trials._x000D_
_x000D_
Our team will identify important elements that researchers, funders, and other stakeholders should reflect on when considering moving a cell therapy to evaluation in humans for the first time. We are currently conducting comprehensive reviews to understand a) how clinicians decide when to test a new therapy in humans, and b) requirements in regulatory documents for approving this testing. Next, we plan to conduct interviews with clinician and regulatory authors of these documents. This will give us a better understanding of their work. We will use our results to draft guidance on important features for researchers testing new treatments in animals to consider. We will then refine this guidance with input from key stakeholders. This guidance will help improve the quality of decision making when considering which cell therapies should be advanced to clinical trials. |
01/01/1970 |
01/01/1970 |
| 2023 |
Colin Crist (P) |
Sir Mortimer B. Davis-Jewish General Hospital |
Subventions de soutien aux projets à fort impact |
Crist |
Chercheur principal |
Colin Crist |
250 000 |
Shining light on muscle regeneration: MuSC mediated delivery of optogenetic contractile properties to skeletal muscle |
Maladie musculaire, maladies musculaires |
Muscle stem cell, ex vivo expansion, genetic manipulation, channelrhodopsin, optogenetics |
Skeletal muscle is required for all voluntary movement and is also an important thermogenic organ in adult vertebrates. Although skeletal muscle has a remarkable muscle stem cell (MuSC) dependent capacity for regeneration, it is subject to several diseases, including a large family of muscular dystrophies as well as muscle wasting associated with cancer (cachexia) and aging (sarcopenia). Moreover, loss of muscle strength and paralysis of specific muscle groups can endure in survivors of stroke and spinal cord injury. New therapeutic strategies to restore muscle function are urgently needed._x000D_
_x000D_
Cell based therapies for muscle disease have been envisioned for decades. Although early clinical trials suggest that donor cell transplantation by intramuscular injection is safe, three major hurdles need to be overcome include our inability to expand rare muscle stem cells (MuSCs, the cells that are normally responsible for lifelong regeneration of skeletal muscle), inability to deliver donor myogenic cells systemically through the blood stream, and poor mobility of MuSCs from sites of intramuscular injection. _x000D_
_x000D_
Our vision is to engineer designer, off-the-shelf MuSCs that will evade immune surveillance, engraft into skeletal muscle and turn the myofibre into a therapeutic molecule synthesis platform. Our mission is to take advantage of our MuSC expansion conditions to generate designer MuSCs that will impart contractile properties to skeletal muscle when stimulated with light. |
01/01/1970 |
01/01/1970 |
| 2023 |
Zachary Laksman (P) |
University of British Columbia |
Subventions de soutien aux projets à fort impact |
Laksman |
Chercheur principal |
Zachary Laksman |
249 997 |
Development of high-throughput assays to stratify cardiotoxic drug risk by sex and genotype |
Maladies cardiaques, maladie cardiaque, maladies du cœur |
drug safety, drug development, personalized medicine, tissue engineering, translational medicine, genetic heart disease |
An important consideration in the development of new medications is side effects. If new drugs are tested and found to affect the heart, those drugs are not considered safe. We will make more accurate tests for the side effects of drugs on the heart. To do this, we will use a “heart in a dish” model to test drugs. In this model, we engineer heart cells so that we can study how they beat in the dish, and how the beat changes in response to drugs._x000D_
Our model will be an improvement on earlier work in several ways. It will use cells that are more like the cells found in adult hearts. We will separately test both male and female cells. We will consider the roles of increased heart rate and the strength of contraction of the beating cells. We will also test whether a very common mutation changes how the cells respond to drugs. In the future, we will be able to test for personalized responses to drugs. This will make medications safer for everybody. _x000D_ |
01/01/1970 |
01/01/1970 |
| 2023 |
Yale Michaels (P) |
CancerCare Manitoba |
Subventions de soutien aux projets à fort impact |
Michaels |
Chercheur principal |
Yale Michaels, David Knapp |
185 290 |
Cellular engineering to enhance T cell production from pluripotent stem cells |
Immunothérapie; cancer |
Synthetic biology, immunotherapy, haematopoiesis, genome engineering |
T cells are a type of immune cell that protects us from infection. T cells can also be used to treat diseases such as cancer. T cells are removed from a patient’s blood and genetically modified so that they can recognize and kill cancer cells before being returned to the patient’s body. These engineered T cell therapies are very effective with cure-rates above 50% for some types of blood cancer but they are also extremely expensive, costing about $500,000 per patient. To make these treatments cheaper, scientists are trying to produce T cells in the lab from stem cells using a process called in vitro differentiation. By making large quantities of T cells from stem cells in the lab, we can make one product to treat many patients, a much cheaper approach than manufacturing a new personal T cell therapy for each individual. The goal of our project is to make in vitro differentiation more efficient and less expensive so we can bring down the overall cost of T cell therapy and help more patients access these life-saving treatments. Previously, stem cells have been turned into T cells by feeding them complex formulas of proteins and small molecules. Our team is using our expertise in gene editing to make genetically engineered stem cells that know how to become T cells with a reduced reliance on expensive proteins. Our work will contribute to cheaper T cell manufacturing and build Canadian scientific excellence in genetic engineering of stem cells. |
01/01/1970 |
01/01/1970 |
| 2023 |
David Knapp (C) |
Université de Montréal |
Subventions de soutien aux projets à fort impact |
Michaels |
Cochercheur |
Yale Michaels, David Knapp |
64 667 |
Cellular engineering to enhance T cell production from pluripotent stem cells |
Immunothérapie; cancer |
Synthetic biology, immunotherapy, haematopoiesis, genome engineering |
T cells are a type of immune cell that protects us from infection. T cells can also be used to treat diseases such as cancer. T cells are removed from a patient’s blood and genetically modified so that they can recognize and kill cancer cells before being returned to the patient’s body. These engineered T cell therapies are very effective with cure-rates above 50% for some types of blood cancer but they are also extremely expensive, costing about $500,000 per patient. To make these treatments cheaper, scientists are trying to produce T cells in the lab from stem cells using a process called in vitro differentiation. By making large quantities of T cells from stem cells in the lab, we can make one product to treat many patients, a much cheaper approach than manufacturing a new personal T cell therapy for each individual. The goal of our project is to make in vitro differentiation more efficient and less expensive so we can bring down the overall cost of T cell therapy and help more patients access these life-saving treatments. Previously, stem cells have been turned into T cells by feeding them complex formulas of proteins and small molecules. Our team is using our expertise in gene editing to make genetically engineered stem cells that know how to become T cells with a reduced reliance on expensive proteins. Our work will contribute to cheaper T cell manufacturing and build Canadian scientific excellence in genetic engineering of stem cells. |
01/01/1970 |
01/01/1970 |
| 2023 |
Martin Post (P) |
Hospital for Sick Children |
Subventions de soutien aux projets à fort impact |
Post |
Chercheur principal |
Martin Post, Andras Nagy |
215 960 |
Enhancing the production of human alveolar-like macrophages for lung cancer therapy |
Maladie pulmonaire, maladies pulmonaires, maladie des poumons, maladies des poumons |
Alveolar macrophages, lung cancer, proliferation, genetic modification, phagocytosis, SIRPalpha |
We have made specialized immune cells from animal stem cells that can clean up diseased cells, viruses, and bacteria in the airways of mice and improve short and long-term lung disease outcomes. We have also made these specialized immune cells from human stem cells. Cell growth of human immune cells slows over time; therefore, to scale our production to clinically relevant cell numbers for human use, we will temporarily change these immune cells into faster growing pre-immune cells by insertion of specific genes that can be switched on and off. Switching them on for a defined time will lead to a large pool of these cells that then can be converted back to the original immune cells. Our aim is to use these cells to target, kill and clear solid lung cancer tumours. To accomplish this, the human immune cells will be modified to display a mutant protein on their cell surface that allows the immune cell to interact, kill and remove tumour cells. We have shown in similar animal-derived immune cells that this modification promotes tumour cell death and removal. We will test the killing capacity of these modified human immune cells by culturing them together with patient-derived cancer cells that are grown in a 3D organ-like structure. This will determine the efficacy of our new immune-cell technology for targeting solid lung tumours, an area of cancer research that has lacked innovation for several decades despite very poor survival rates and a high healthcare burden in Canada. |
01/01/1970 |
01/01/1970 |
| 2023 |
Andras Nagy (C) |
Sinai Health System |
Subventions de soutien aux projets à fort impact |
Post |
Cochercheur |
Martin Post, Andras Nagy |
34 040 |
Enhancing the production of human alveolar-like macrophages for lung cancer therapy |
Maladie pulmonaire, maladies pulmonaires, maladie des poumons, maladies des poumons |
Alveolar macrophages, lung cancer, proliferation, genetic modification, phagocytosis, SIRPalpha |
We have made specialized immune cells from animal stem cells that can clean up diseased cells, viruses, and bacteria in the airways of mice and improve short and long-term lung disease outcomes. We have also made these specialized immune cells from human stem cells. Cell growth of human immune cells slows over time; therefore, to scale our production to clinically relevant cell numbers for human use, we will temporarily change these immune cells into faster growing pre-immune cells by insertion of specific genes that can be switched on and off. Switching them on for a defined time will lead to a large pool of these cells that then can be converted back to the original immune cells. Our aim is to use these cells to target, kill and clear solid lung cancer tumours. To accomplish this, the human immune cells will be modified to display a mutant protein on their cell surface that allows the immune cell to interact, kill and remove tumour cells. We have shown in similar animal-derived immune cells that this modification promotes tumour cell death and removal. We will test the killing capacity of these modified human immune cells by culturing them together with patient-derived cancer cells that are grown in a 3D organ-like structure. This will determine the efficacy of our new immune-cell technology for targeting solid lung tumours, an area of cancer research that has lacked innovation for several decades despite very poor survival rates and a high healthcare burden in Canada. |
01/01/1970 |
01/01/1970 |
| 2023 |
Arvind Mer (P) |
Université d’Ottawa |
Subventions de soutien aux projets à fort impact |
Mer |
Chercheur principal |
Arvind Mer, Alexandre Blais |
144 000 |
Decoding Alternative Splicing Regulatory Networks in Myogenic Stem Cell Function |
Maladie musculaire, maladies musculaires |
Muscle Stem Cells, Satellite Cells, Isoforms, Alternative Splicing, Machine learning, Pharmacogenomics, Bioinformatics, Gene Expression Profiling |
Muscle stem cells also known as satellite cells are critical components of skeletal muscle repair after injury. In healthy tissue, satellite cells are undifferentiated and quiescent. Upon injury, they respond quickly and become activated, start proliferation, and differentiate to generate new cells that replace injured cells. Furthermore, a small fraction of the satellite cells will be generated for future use, by avoiding differentiation and returning to the quiescent state. Multiple regulatory mechanisms tightly control each step of this process. However, a key problem in the field is that we don’t fully understand how these fates (quiescence, activation, differentiation, self-renewal) are established, or what mechanisms determine which fate a cell will adopt. Our research addresses these fundamental questions by using bioinformatics, machine learning and experimental genomics approach. We aim to decipher how the process of alternative splicing regulates satellite cells' activity. Furthermore, we will use machine learning to prioritize drugs that can activate satellite cells and maintain their regeneration potential for the long term. This will have a direct implication in the field of regenerative medicine. |
01/01/1970 |
01/01/1970 |
| 2023 |
Alexandre Blais (C) |
Université d’Ottawa |
Subventions de soutien aux projets à fort impact |
Mer |
Cochercheur |
Arvind Mer, Alexandre Blais |
106 000 |
Decoding Alternative Splicing Regulatory Networks in Myogenic Stem Cell Function |
Maladie musculaire, maladies musculaires |
Muscle Stem Cells, Satellite Cells, Isoforms, Alternative Splicing, Machine learning, Pharmacogenomics, Bioinformatics, Gene Expression Profiling |
Muscle stem cells also known as satellite cells are critical components of skeletal muscle repair after injury. In healthy tissue, satellite cells are undifferentiated and quiescent. Upon injury, they respond quickly and become activated, start proliferation, and differentiate to generate new cells that replace injured cells. Furthermore, a small fraction of the satellite cells will be generated for future use, by avoiding differentiation and returning to the quiescent state. Multiple regulatory mechanisms tightly control each step of this process. However, a key problem in the field is that we don’t fully understand how these fates (quiescence, activation, differentiation, self-renewal) are established, or what mechanisms determine which fate a cell will adopt. Our research addresses these fundamental questions by using bioinformatics, machine learning and experimental genomics approach. We aim to decipher how the process of alternative splicing regulates satellite cells' activity. Furthermore, we will use machine learning to prioritize drugs that can activate satellite cells and maintain their regeneration potential for the long term. This will have a direct implication in the field of regenerative medicine. |
01/01/1970 |
01/01/1970 |
| 2023 |
Shinichiro Ogawa (P) |
University Health Network |
Subventions de soutien aux projets à fort impact |
Ogawa |
Chercheur principal |
Shinichiro Ogawa, Boyang Zhang |
158 433 |
Sustained liver engraftment with bioengineered functionally complete liver tissues |
Maladies du foie, maladie du foie, maladie hépatique |
Liver regeneration, human pluripotent stem cell- derived hepatocytes, intrahepatic engraftment |
Liver failure can only be treated with a new liver; however, many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Despite the recent progress in stem cell therapy, liver cells produced from stem cells are still dissimilar to adult liver cells in terms of maturity and function and thus engraft poorly in injured livers. Recognizing stem cell-derived liver cells cannot further function as single cells, we propose developing functionally complete liver tissues that place the liver cells in their native environment to support their continuous function and engraftment. We are taking an integrated approach that involves directed stem cell differentiation and bioengineered tissue assembly to develop the first functionally complete liver tissue that will possess perfusable blood vessels for nutrient delivery, bile ductal networks for bile acid clearance. We will demonstrate the long-term sustained engraftment of our engineered liver, overcoming the existing low efficacy in stem cell-based liver regenerative therapy. Beyond regenerative medicine, the developed platform and tissues will also find broad applications in drug toxicity and metabolism screening. Ultimately, this work will provide the foundation for the successful clinical translation of stem cell therapy to Canadians living with liver diseases. |
01/01/1970 |
01/01/1970 |
| 2023 |
Boyang Zhang (C) |
McMaster University |
Subventions de soutien aux projets à fort impact |
Ogawa |
Cochercheur |
Shinichiro Ogawa, Boyang Zhang |
90 800 |
Sustained liver engraftment with bioengineered functionally complete liver tissues |
Maladies du foie, maladie du foie, maladie hépatique |
Liver regeneration, human pluripotent stem cell- derived hepatocytes, intrahepatic engraftment |
Liver failure can only be treated with a new liver; however, many patients die waiting for a transplant. Using stem cells to create new liver cells is a promising way to restore liver function. Despite the recent progress in stem cell therapy, liver cells produced from stem cells are still dissimilar to adult liver cells in terms of maturity and function and thus engraft poorly in injured livers. Recognizing stem cell-derived liver cells cannot further function as single cells, we propose developing functionally complete liver tissues that place the liver cells in their native environment to support their continuous function and engraftment. We are taking an integrated approach that involves directed stem cell differentiation and bioengineered tissue assembly to develop the first functionally complete liver tissue that will possess perfusable blood vessels for nutrient delivery, bile ductal networks for bile acid clearance. We will demonstrate the long-term sustained engraftment of our engineered liver, overcoming the existing low efficacy in stem cell-based liver regenerative therapy. Beyond regenerative medicine, the developed platform and tissues will also find broad applications in drug toxicity and metabolism screening. Ultimately, this work will provide the foundation for the successful clinical translation of stem cell therapy to Canadians living with liver diseases. |
01/01/1970 |
01/01/1970 |
| 2023 |
Kristin Hope (P) |
University Health Network |
Subventions de soutien aux projets à fort impact |
Hope |
Chercheur principal |
Kristin Hope |
250 000 |
Harnessing developmentally-guided post-transcriptional HSC drivers to advance in vivo hematopoietic regeneration |
Greffe de moelle osseuse |
hematopoietic stem cells, in vivo regeneration, xenotransplantation, RNA binding proteins, self-renewal, HSC exhaustion |
Blood stem cells carefully control the cells they produce over time, choosing to replicate themselves or make functional blood cells (white & red blood cells, platelets, etc) depending on bodily needs. While adult blood stem cells keep their numbers steady to maintain a healthy blood system, fetal stem cells are hardwired to replicate themselves to establish a stem cell pool that can sustain the blood system throughout life. What controls this early replicative process is poorly understood, but represent an untapped system for promoting much-needed, lifesaving adult stem cell replenishment following blood system-damaging treatments and physiological insults such as chemotherapy, blood stem cell transplant, and infection. We have identified the protein TRIM71 as a potential driver of fetal blood stem cell replication and aim to test if its restoration in adult blood stem cells will encourage their expansion and re-establish blood system maintenance. Using pre-clinical models of blood stem cell defects and characterizing clinical samples that are real-world examples of blood stem cell exhaustion resulting from therapeutic insults we aim to unravel how TRIM71 works to promote stem cells and identify drugs that can mimic these effects. This study will culminate in the identification of new targets for re-establishment of the blood stem cell pool across a wide group of adult patients and ultimately address clinically unmet needs of hematological regenerative medicine therapies. |
01/01/1970 |
01/01/1970 |
| 2023 |
Junio Dort (P) |
Université d’Ottawa |
Subventions de soutien aux projets à fort impact |
Dort |
Chercheur principal |
Junio Dort |
250 000 |
Novel therapeutic compounds targeting G-coupled receptors to enhance muscle stem cell function in Duchenne muscular dystrophy |
Maladie musculaire, maladies musculaires |
Muscle stem cells, regeneration, G-protein-coupled receptor, differentiation, Duchenne muscular dystrophy |
Duchenne muscular dystrophy (DMD), a frequent genetic disease affecting young boys, causes severe muscle wasting, resulting in ambulatory and respiratory impairments, and premature death. This degenerative environment leads to chronic inflammation that accelerates muscle wasting. Glucocorticoids remain the most efficient drugs that reduce the progression of the disease; however, its positive effect is limited to a few years. Glucocorticoids also have many detrimental side effects. A class of pharmacological compounds called ‘bioactive lipid receptor agonists’ could represent the future of the conventional treatment for DMD. In various inflammatory diseases, the use of these compounds decreases inflammation without harmful side effects. But the therapeutic effect of these compounds is not known on skeletal muscle. The objective of this research project is to investigate the efficacity of these compounds to repair muscles affected by DMD. We will use cells from dystrophic mice and from patients with DMD, as well as the mdx-DBA/2J mice (a well characterized model of DMD) to characterize the beneficial effect of these compounds compared to glucocorticoids. This research project will demonstrate the efficacy of bioactive lipid receptor agonists to reduce inflammation and enhance muscle repair. This will clearly contribute to the development of a more potent treatment for DMD as compared to glucocorticoids. |
01/01/1970 |
01/01/1970 |
| 2023 |
Yan Burelle (P) |
Université d’Ottawa |
Subventions de soutien aux projets à fort impact |
Burelle |
Chercheur principal |
Yan Burelle |
224 520 |
Targeting mitochondrial quality control to promote muscle regeneration. |
Maladie musculaire, maladies musculaires |
Muscle stem cells, mitochondria, mitophagy, fate decision, differentiation, muscle regeneration |
Dysfunction of mitochondria, the cellular powerhouses, plays an important role in a plethora human disorders, including rare genetic myopathies such as Duchenne Muscular Dystrophy (DMD). Mitochondrial dysfunction also causes stem cell abnormalities in several tissues including skeletal muscle. For this reason, modulation of mitochondrial quality is increasingly proposed as a therapeutic strategy to prevent/restore cellular function. However, our ability to do so in muscle stem cells (MuSCs) is hampered by limited knowledge of pathways regulating mitochondrial quality._x000D_
The proposed work will define how mitophagy (a process degrading damaged mitochondria), is regulated in MuSCs, what pathways are involved, how it affects mitochondrial qualities and MuSC function, and whether mitophagy can be targeted to better maintain muscle regeneration capacity._x000D_
_x000D_
Three aims are proposed. _x000D_
1) Delineate the role of mitophagy in the maintenance of MuSC regenerative capacity by silencing the expression of Parkin, a key gene regulating mitophagy._x000D_
2) Determine the effect of genetically enhancing mitophagy on MuSC regenerative capacity_x000D_
3) Determine the effect of novel mitophagy stimulating drugs MuSC regenerative capacity_x000D_
_x000D_
This work will clearly establish the role of mitophagy in MuSCs, and provide proof-of-principle data on the therapeutic potential of a novel class of mitophagy enhancers to improve muscle regeneration. |
01/01/1970 |
01/01/1970 |
| 2023 |
James Ellis (P) |
Hospital for Sick Children |
Subventions de soutien aux projets à fort impact |
Ellis |
Chercheur principal |
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh |
130 000 |
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons |
Trouble du cerveau, troubles du cerveau |
iPSC, NPC, astrocytes, Extracellular Vesicles, neurons |
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_ |
01/01/1970 |
01/01/1970 |
| 2023 |
Augusto Zani (C) |
Hospital for Sick Children |
Subventions de soutien aux projets à fort impact |
Ellis |
Cochercheur |
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh |
70 000 |
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons |
Trouble du cerveau, troubles du cerveau |
iPSC, NPC, astrocytes, Extracellular Vesicles, neurons |
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_ |
01/01/1970 |
01/01/1970 |
| 2023 |
Ji-Young Youn (C) |
Hospital for Sick Children |
Subventions de soutien aux projets à fort impact |
Ellis |
Cochercheur |
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh |
25 000 |
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons |
Trouble du cerveau, troubles du cerveau |
iPSC, NPC, astrocytes, Extracellular Vesicles, neurons |
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_ |
01/01/1970 |
01/01/1970 |
| 2023 |
Karun Singh (C) |
University Health Network |
Subventions de soutien aux projets à fort impact |
Ellis |
Cochercheur |
James Ellis, Augusto Zani, Ji-Young Youn, Karun Singh |
25 000 |
Extracellular vesicles transport molecular cargo from stem cell derived healthy astrocytes to rescue Rett syndrome neurons |
Trouble du cerveau, troubles du cerveau |
iPSC, NPC, astrocytes, Extracellular Vesicles, neurons |
Rett syndrome (RTT) affects girls and compromises how the brain develops. RTT babies develop normally for up to 18 months, but then lose communication skills, movement and coordination abilities. Brain cells called neurons have shorter extensions and fewer connections with other neurons in RTT. Astrocytes, the support cells of the brain, are also affected by RTT and fail to support connections between neurons. We looked at one way cells communicate with each other by releasing small droplets called extracellular vesicles, or EVs. EVs carry cargo in the form of proteins and genetic material like miRNAs. EVs deliver their cargo to nearby neurons or directly into the bloodstream. EV cargo contents can change the way target cells behave._x000D_
Studies suggest that EVs from healthy astrocytes and neurons can be used to reverse the activity of RTT neurons. We plan to isolate healthy astrocyte EVs from stem cells, administer them to RTT and healthy neurons, and study if they rescue RTT neuron network and activity. We will determine what protein cargo is present in the EVs, discover which genes become activated or silenced in EV treated RTT neurons, and find out if EVs can help normal neurons mature in a dish. Our findings will help improve neuron culture methods for regenerative medicine studies, identify EV cargo found in the blood that can indicate if a RTT patient is responding to a new treatment, and EVs themselves may be a future therapy for RTT._x000D_
_x000D_ |
01/01/1970 |
01/01/1970 |
| 2025 |
Benjamin Haley (C) |
CIUSSS de l'Est-de-l'Île-de-Montréal (Hôpital Maisonneuve-Rosemont) |
Subvention de soutien à l'accélération de la transposition clinique |
Sauvageau |
Cochercheur |
Benjamin Haley, Guy Sauvageau, Jean-Sébastien Delisle, Kelly McNagny |
75,000.00 |
Accelerating clinical translation of UM171 expanded and epitope-engineered HSC grafts |
Cancer |
Ingénierie des épitopes, UM171, greffe de sang de cordon, édition génique, immunothérapie, translation clinique |
Acute Myeloid Leukemia (AML) is a severe form of blood cancer with limited treatment options, especially for patients who relapse or are at high risk. While immunotherapies show promise, they often damage healthy blood stem cells, making it challenging to target leukemia effectively and without major side-effects. Our research addressed this issue by developing a cutting-edge therapy that combines gene editing and UM171, a molecule that can multiply blood stem cells in culture. This approach protects stem cell grafts from the toxic effects of immunotherapy while maintaining their ability to fight leukemia. With funding from the SCN Horizon program, we engineered a small genetic change in a key protein, CD33, that prevents it from being targeted by certain AML treatments, like gemtuzumab ozogamicin (Mylotarg). Introduction of this genetic change in healthy stem cells fully protects them from immunotherapies following transplantation while preserving the graft’s cancer-fighting power. Our therapy shows great promise, offering hope to patients with poor outcomes, such as those with adverse genetic mutations or prior transplant failures. To bring this treatment to patients, we will focus on safety, efficient manufacturing, and ensuring regulatory approval, paving the way for clinical trials and future use in practice. This work represents a significant step toward better, safer treatments for AML |
01/01/1970 |
31/03/2027 |
| 2025 |
Guy Sauvageau (P) |
Université de Montréal |
Subvention de soutien à l'accélération de la transposition clinique |
Sauvageau |
Chercheur principal |
Benjamin Haley, Guy Sauvageau, Jean-Sébastien Delisle, Kelly McNagny |
450,000.00 |
Accelerating clinical translation of UM171 expanded and epitope-engineered HSC grafts |
Cancer |
Ingénierie des épitopes, UM171, greffe de sang de cordon, édition génique, immunothérapie, translation clinique |
Acute Myeloid Leukemia (AML) is a severe form of blood cancer with limited treatment options, especially for patients who relapse or are at high risk. While immunotherapies show promise, they often damage healthy blood stem cells, making it challenging to target leukemia effectively and without major side-effects. Our research addressed this issue by developing a cutting-edge therapy that combines gene editing and UM171, a molecule that can multiply blood stem cells in culture. This approach protects stem cell grafts from the toxic effects of immunotherapy while maintaining their ability to fight leukemia._x000D_
_x000D_
With funding from the SCN Horizon program, we engineered a small genetic change in a key protein, CD33, that prevents it from being targeted by certain AML treatments, like gemtuzumab ozogamicin (Mylotarg). Introduction of this genetic change in healthy stem cells fully protects them from immunotherapies following transplantation while preserving the graft’s cancer-fighting power._x000D_
_x000D_
Our therapy shows great promise, offering hope to patients with poor outcomes, such as those with adverse genetic mutations or prior transplant failures. To bring this treatment to patients, we will focus on safety, efficient manufacturing, and ensuring regulatory approval, paving the way for clinical trials and future use in practice. This work represents a significant step toward better, safer treatments for AML._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Jean-Sébastien Delisle (C) |
CIUSSS de l'Est-de-l'Île-de-Montréal (Hôpital Maisonneuve-Rosemont) |
Subvention de soutien à l'accélération de la transposition clinique |
Sauvageau |
Cochercheur |
Benjamin Haley, Guy Sauvageau, Jean-Sébastien Delisle, Kelly McNagny |
75,000.00 |
Accelerating clinical translation of UM171 expanded and epitope-engineered HSC grafts |
Cancer |
Ingénierie des épitopes, UM171, greffe de sang de cordon, édition génique, immunothérapie, translation clinique |
Acute Myeloid Leukemia (AML) is a severe form of blood cancer with limited treatment options, especially for patients who relapse or are at high risk. While immunotherapies show promise, they often damage healthy blood stem cells, making it challenging to target leukemia effectively and without major side-effects. Our research addressed this issue by developing a cutting-edge therapy that combines gene editing and UM171, a molecule that can multiply blood stem cells in culture. This approach protects stem cell grafts from the toxic effects of immunotherapy while maintaining their ability to fight leukemia._x000D_
_x000D_
With funding from the SCN Horizon program, we engineered a small genetic change in a key protein, CD33, that prevents it from being targeted by certain AML treatments, like gemtuzumab ozogamicin (Mylotarg). Introduction of this genetic change in healthy stem cells fully protects them from immunotherapies following transplantation while preserving the graft’s cancer-fighting power._x000D_
_x000D_
Our therapy shows great promise, offering hope to patients with poor outcomes, such as those with adverse genetic mutations or prior transplant failures. To bring this treatment to patients, we will focus on safety, efficient manufacturing, and ensuring regulatory approval, paving the way for clinical trials and future use in practice. This work represents a significant step toward better, safer treatments for AML._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Kelly McNagny (C) |
University of British Columbia |
Subvention de soutien à l'accélération de la transposition clinique |
Sauvageau |
Cochercheur |
Benjamin Haley, Guy Sauvageau, Jean-Sébastien Delisle, Kelly McNagny |
50,000.00 |
Accelerating clinical translation of UM171 expanded and epitope-engineered HSC grafts |
Cancer |
Ingénierie des épitopes, UM171, greffe de sang de cordon, édition génique, immunothérapie, translation clinique |
Acute Myeloid Leukemia (AML) is a severe form of blood cancer with limited treatment options, especially for patients who relapse or are at high risk. While immunotherapies show promise, they often damage healthy blood stem cells, making it challenging to target leukemia effectively and without major side-effects. Our research addressed this issue by developing a cutting-edge therapy that combines gene editing and UM171, a molecule that can multiply blood stem cells in culture. This approach protects stem cell grafts from the toxic effects of immunotherapy while maintaining their ability to fight leukemia._x000D_
_x000D_
With funding from the SCN Horizon program, we engineered a small genetic change in a key protein, CD33, that prevents it from being targeted by certain AML treatments, like gemtuzumab ozogamicin (Mylotarg). Introduction of this genetic change in healthy stem cells fully protects them from immunotherapies following transplantation while preserving the graft’s cancer-fighting power._x000D_
_x000D_
Our therapy shows great promise, offering hope to patients with poor outcomes, such as those with adverse genetic mutations or prior transplant failures. To bring this treatment to patients, we will focus on safety, efficient manufacturing, and ensuring regulatory approval, paving the way for clinical trials and future use in practice. This work represents a significant step toward better, safer treatments for AML._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Cindi Morshead (C) |
University of Toronto |
Subvention de soutien à l'accélération de la transposition clinique |
Shoichet |
Cochercheuse |
Cindi Morshead, Douglas Cook, Molly Shoichet |
71,254.00 |
Sustained, Local Delivery of Re-engineered Chondroitinase ABC to the Central Nervous System after Traumatic Injury |
Troubles neurologiques |
Plasticité neuronale, régénération du cerveau, administration locale, libération prolongée, produits thérapeutiques exclusifs, AVC, lésion de la moelle épinière |
Stroke injury is devastating, with few therapeutic options other than rehabilitation. After stroke, an aggregate scar forms that limits tissue degeneration after the initial insult, which is good; yet, this same scar also inhibits tissue regeneration after the injury has stabilized, which is bad.
We propose to degrade this scar tissue after stroke and thereby promote tissue regeneration and functional repair in combination with rehabilitation. We invented a novel enzyme and a way to deliver it locally for a sustained period to the brain.
We will: advance the manufacturing of our product in a GMP facility (with manufacturing experts) and then test this product in models of stroke. At the same time, we will work with regulatory experts to connect with Health Canada with the goal of advancing towards a first-in-human clinical trial.
We bring together experts in bioengineering, neuroscience and neurosurgery with international collaborators with complementary experience.
In Canada alone, strokes costs $10.9 billion/year. A therapeutic product that puts a dent in these costs would have enormous health and economic benefit. |
01/01/1970 |
31/03/2027 |
| 2025 |
Douglas Cook (C) |
Queen's University |
Subvention de soutien à l'accélération de la transposition clinique |
Shoichet |
Cochercheuse |
Cindi Morshead, Douglas Cook, Molly Shoichet |
181,320.00 |
Sustained, Local Delivery of Re-engineered Chondroitinase ABC to the Central Nervous System after Traumatic Injury |
Troubles neurologiques |
Plasticité neuronale, régénération du cerveau, administration locale, libération prolongée, produits thérapeutiques exclusifs, AVC, lésion de la moelle épinière |
Stroke injury is devastating, with few therapeutic options other than rehabilitation. After stroke, an aggregate scar forms that limits tissue degeneration after the initial insult, which is good; yet, this same scar also inhibits tissue regeneration after the injury has stabilized, which is bad.
We propose to degrade this scar tissue after stroke and thereby promote tissue regeneration and functional repair in combination with rehabilitation. We invented a novel enzyme and a way to deliver it locally for a sustained period to the brain.
We will: advance the manufacturing of our product in a GMP facility (with manufacturing experts) and then test this product in models of stroke. At the same time, we will work with regulatory experts to connect with Health Canada with the goal of advancing towards a first-in-human clinical trial.
We bring together experts in bioengineering, neuroscience and neurosurgery with international collaborators with complementary experience.
In Canada alone, strokes costs $10.9 billion/year. A therapeutic product that puts a dent in these costs would have enormous health and economic benefit. |
01/01/1970 |
31/03/2027 |
| 2025 |
Molly Shoichet (P) |
University of Toronto |
Subvention de soutien à l'accélération de la transposition clinique |
Shoichet |
Chercheuse principale |
Cindi Morshead, Douglas Cook, Molly Shoichet |
397,390.00 |
Sustained, Local Delivery of Re-engineered Chondroitinase ABC to the Central Nervous System after Traumatic Injury |
Troubles neurologiques |
Plasticité neuronale, régénération du cerveau, administration locale, libération prolongée, produits thérapeutiques exclusifs, AVC, lésion de la moelle épinière |
Stroke injury is devastating, with few therapeutic options other than rehabilitation. After stroke, an aggregate scar forms that limits tissue degeneration after the initial insult, which is good; yet, this same scar also inhibits tissue regeneration after the injury has stabilized, which is bad.
We propose to degrade this scar tissue after stroke and thereby promote tissue regeneration and functional repair in combination with rehabilitation. We invented a novel enzyme and a way to deliver it locally for a sustained period to the brain.
We will: advance the manufacturing of our product in a GMP facility (with manufacturing experts) and then test this product in models of stroke. At the same time, we will work with regulatory experts to connect with Health Canada with the goal of advancing towards a first-in-human clinical trial.
We bring together experts in bioengineering, neuroscience and neurosurgery with international collaborators with complementary experience.
In Canada alone, strokes costs $10.9 billion/year. A therapeutic product that puts a dent in these costs would have enormous health and economic benefit. |
01/01/1970 |
31/03/2027 |
| 2025 |
Bernard Thébaud (P) |
Institut de recherche de l'Hôpital d'Ottawa |
Subvention de soutien à l'accélération de la transposition clinique |
Thébaud |
Chercheur principal |
Bernard Thebaud |
649,333.00 |
AAVenger-B: Adeno-Associated Virus Engineered Epithelial progenitor cell Regeneration for surfactant protein B deficiency |
Troubles pulmonaires |
Régénération, cellules progénitrices pulmonaires, lésion pulmonaire, thérapie génique, virus adéno-associé (AAV), fabrication, bioingénierie |
One million Canadians, many of them children, live with life-limiting rare genetic diseases. Only 6% of these diseases have a treatment. Genetic lung diseases can affect babies right at birth causing trouble to breathe and the need for mechanical ventilation to keep these babies alive. Gene therapy offers a promising solution by addressing the root cause of genetic diseases. Gene therapy uses a shuttle (vector) to bring the healthy version of the gene into the lung. We made a new and improved shuttle that is particularly good at targeting the exact lung cell to deliver the healthy gene and save lives. Here we propose to produce the first lung gene therapy following a Good Manufacturing Practice-compliant process for vector production to obtain Health Canada approval for a clinical trial in patients. The impact of our research lies in its potential to revolutionize the treatment of genetic lung diseases including cystic fibrosis, and to serve as a model for successful laboratory bench to bedside translation for many other genetic disorders to improve the health of the many patients with these rare but life-limiting diseases. In addition, our innovation will deliver economic and social benefits for Canadians through new patents, commercialization and job creation. |
01/01/1970 |
31/03/2027 |
| 2025 |
Sandra Cohen (P) |
CIUSSS de l'Est-de-l'Île-de-Montréal (Hôpital Maisonneuve-Rosemont) |
Subvention de subvention des essais cliniques |
Cohen |
Chercheuse principale |
Sandra Cohen |
1,100,000.00 |
Expanding Balanced-Hematopoietic Stem Cells With Optimized Dose of UM171 to Improve Engraftment |
Cancer |
Greffe de cellules souches, UM171, effet lié à la dose, lymphopoïèse, prise de greffe, sang de cordon |
Cord blood transplantation (CBT) is a crucial treatment for patients with blood cancers who lack a fully matched donor. It is associated with lower relapse rates but is limited by the small number of cells in cord blood (CB), Chercheur principaling to slower recovery and a higher risk of complications. UM171, a groundbreaking discovery by our team, expands stem cells in CB and has already shown in clinical trials to reduce deaths from CBT and enable recovery times comparable to standard transplants._x000D_
Emerging research suggests that using higher doses of UM171 could improve outcomes further by speeding up recovery and enhancing immune system rebuilding. To explore this potential, we are launching a new clinical trial to test this hypothesis._x000D_
This trial will involve 7 patients aged 18-67 with high-risk blood cancers or no matched donor. Patients will receive either high- or reduced-intensity chemotherapy, followed by a UM171-expanded CBT. The UM171 dose will progressively increase if initial patients show quicker recovery._x000D_
Safety will be rigorously monitored, focusing on white blood cell recovery, complications, survival, and immune system restoration. Patients will be followed for 12 months. This study aims to confirm that higher doses of UM171 can accelerate recovery, strengthen the immune system, and reduce hospital stays, making CBT a more accessible and effective treatment for patients with limited options. |
01/01/1970 |
31/03/2028 |
| 2025 |
Lucie Germain (P) |
Université Laval |
Subvention de subvention des essais cliniques |
Germain |
Chercheuse principale |
Lucie Germain |
662,470.00 |
Clinical trial for dystrophic epidermolysis bullosa (EB) using GMEB-SASS, a genetically modified EB skin substitute |
Guérison des plaies |
Maladie rare, greffe de peau, épidermolyse bulleuse, thérapie génique, substituts cutanés, ingénierie tissulaire, cellules souches |
A rare skin disease called dystrophic epidermolysis bullosa is (RDEB) is a genetic disorder that manifests as a lack of adhesion between the dermis and the epidermis and causes mucosa and epidermal detachments that can Chercheur principal to severe complications. Around 300-500 persons are affected with EB in Canada. Genetically, DEB is caused by the lack of a protein called Collagen VII that normally is promoting adhesion (acting like a “glue”) between the dermis and epidermis. Sometimes, DEB wounds are very painful and can persist for years or become aggressive skin cancer, which is a major cause of death. Until now, the treatment for DEB patients is palliative, mainly by protecting epithelial wounds with bandages, that are very costly and hard to change. The present clinical trial I/II started in the Centre de recherche en organogenèse expérimentale de l’Université Laval/LOEX, CHU de Québec-UL hospital is consisting in the production of skin substitutes (reconstructed skin) from cells of DEB patients, cultured in the laboratory and genetically corrected by gene therapy to provide the missing collagen. The effectiveness and the safety of this treatment was validated on human skin reconstructed in the lab and grafted on animals. The produced skin tissues will be grafted on the EB wounds to replace the lost skin. It is intended to provide permanent skin replacement to DEB patients and improve their quality of life and lower the burden of this disease on the patient and his family. |
01/01/1970 |
31/03/2028 |
| 2025 |
Bernard Thébaud (P) |
Institut de recherche de l'Hôpital d'Ottawa |
Subvention de subvention des essais cliniques |
Thébaud |
Chercheur principal |
Bernard Thebaud |
1,099,882.00 |
Helping Underdeveloped Lungs with Cells (HULC-2): A randomized controlled trial of MSCs to cut lung injury in preterm infants |
Troubles pulmonaires |
Essai clinique, thérapies à base de cellules mésenchymateuses stromales, lésion pulmonaire, régénération, prématurité |
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that follows mechanical breathing support and oxygen treatment for acute failure to breathe in babies born too soon (before 28 weeks of gestation instead of 40). BPD is a major complication of prematurity with a long-term burden for infants and their families. Damage to the still developing lung stops the normal growth of the air sacs in the lung that allows the uptake of oxygen and release of waste carbon dioxide. Currently there is no treatment for this disease.
Our lab was one of the first to show that a specific type of cell, called mesenchymal stromal cell (MSC), that can be isolated from the umbilical cord, can repair lungs in laboratory models of BPD. Extensive studies have led to Health Canada approval for our Phase 1 clinical trial that showed the safety of a single intravenous injection of UC-MSCs in extreme preterm infants at high risk of developing BPD.
Here, we propose the next logical step: a Phase 2 trial to test the efficacy and safety of UC-MSCs compared to current standard of care. This will be a Canadian multicentre trial enrolling 168 patients to determine if UC-MSC can reduce the time babies spent on a breathing machine and whether this Chercheur principals to better outcomes for premature babies. This first of its kind phase 2 trial highlights Canada’s position as a Chercheur principaler in innovation and regenerative medicine. |
01/01/1970 |
31/03/2028 |
| 2025 |
Yasaman Aghazadeh (P) |
Institut de recherches cliniques de Montréal (IRCM) |
Subvention de démarrage pour chercheurs en début de carrière |
Aghazadeh |
Chercheuse principale |
Yasaman Aghazadeh |
350,000.00 |
Developing stem cell-derived vasculature with immunomodulatory features to enhance beta cell therapies for type 1 diabetes |
Diabète |
Cellules souches pluripotentes humaines, différenciation, vascularisation, îlots, diabète de type 1 |
Type 1 diabetes (T1D) is caused when the immune system mistakenly destroys the beta cells in the pancreas. The beta cells are the source of insulin, which lowers blood glucose, therefore their destruction Chercheur principals to high glucose levels, which is toxic for other organs. Currently, people with T1D require injections of insulin up to 6 times per day and lifelong, which is burdensome. To develop a long-term treatment, human pluripotent stem cells (hESC) are used which are cells that generate all human tissues such as the beta cells. Currently, these beta cells are in clinical trials and show great promise. However, two issues persist: (1) cell death after transplant, because beta cells cannot connect with vessels to obtain oxygen and nutrients, (2) immune-suppression to prevent rejection of the transplanted cells, but immune-suppression has significant side effects such as cancer, and infections. To prevent cell death, we previously developed vessels and co-transplanted them with beta cells in diabetic mice and showed that by bringing blood the vessels prevented their death. In addition, this method significantly improved glucose sensing and insulin secretion. Here, we propose two strategies to engineer or modify vessels to make them “immune resistant” by preventing the immune cells from migrating from inside the vessel to the beta cells. If successful, this proposal could Chercheur principal to an effective beta cell therapy without the need for immune suppression. |
01/01/1970 |
31/03/2028 |
| 2025 |
Jessica Esseltine (P) |
Memorial University of Newfoundland |
Subvention de démarrage pour chercheurs en début de carrière |
Esseltine |
Chercheuse principale |
Jessica Esseltine, Kathleen Hodgkinson |
290,000.00 |
Two serious cardiac mutations together result in no disease phenotype: serendipitous modifiers? |
Troubles cardiaques |
CSPi, cardiomyocytes, troponine, cardiomyopathie hypertrophique, myocardiopathie dilatée, CRISPR-Cas9 |
Cardiomyopathies are a group of related heart diseases that impact both the heart “pumping” system and the “electrical” system. Cardiomyopathies often result in heart failure and/or sudden cardiac death (SCD). Of the 750,000 Canadians living with heart failure, many will die on the transplant wait list. In addition to environmental and lifestyle influences, cardiomyopathies are often caused by genetic mutations. _x000D_
_x000D_
Everybody has a unique set of thousands of genes. Genes are messages written in the DNA alphabet that tell our cells how to properly function. A disease-causing mutation gives bad information to the cell and can cause the entire organ to fail. Unfortunately, these disease-causing mutations may also be passed on to our children, meaning that these devastating heart diseases can "run" in families. _x000D_
_x000D_
Our research involves two gene mutations that cause heart disease in families across Newfoundland and Labrador (NL). Each mutation alone causes severe heart disease. However, when both mutations occur together in the same person, there is no disease. Our project aims to understand how each disease-causing mutation makes the heart cell sick and to understand why both disease-causing mutations together somehow result in no disease. _x000D_
_x000D_
NL has larger numbers of some disease-causing mutations than other places. NL also has amazing families who are part of the research endeavor. This makes NL one of the best places in the world for research into inherited heart disease. |
01/01/1970 |
31/03/2028 |
| 2025 |
Kathleen Hodgkinson (C) |
Memorial University of Newfoundland |
Subvention de démarrage pour chercheurs en début de carrière |
Esseltine |
Cochercheuse |
Jessica Esseltine, Kathleen Hodgkinson |
60,000.00 |
Two serious cardiac mutations together result in no disease phenotype: serendipitous modifiers? |
Troubles cardiaques |
CSPi, cardiomyocytes, troponine, cardiomyopathie hypertrophique, myocardiopathie dilatée, CRISPR-Cas9 |
Cardiomyopathies are a group of related heart diseases that impact both the heart “pumping” system and the “electrical” system. Cardiomyopathies often result in heart failure and/or sudden cardiac death (SCD). Of the 750,000 Canadians living with heart failure, many will die on the transplant wait list. In addition to environmental and lifestyle influences, cardiomyopathies are often caused by genetic mutations. _x000D_
_x000D_
Everybody has a unique set of thousands of genes. Genes are messages written in the DNA alphabet that tell our cells how to properly function. A disease-causing mutation gives bad information to the cell and can cause the entire organ to fail. Unfortunately, these disease-causing mutations may also be passed on to our children, meaning that these devastating heart diseases can "run" in families. _x000D_
_x000D_
Our research involves two gene mutations that cause heart disease in families across Newfoundland and Labrador (NL). Each mutation alone causes severe heart disease. However, when both mutations occur together in the same person, there is no disease. Our project aims to understand how each disease-causing mutation makes the heart cell sick and to understand why both disease-causing mutations together somehow result in no disease. _x000D_
_x000D_
NL has larger numbers of some disease-causing mutations than other places. NL also has amazing families who are part of the research endeavor. This makes NL one of the best places in the world for research into inherited heart disease. |
01/01/1970 |
31/03/2028 |
| 2025 |
Bowen Li (P) |
University of Toronto |
Subvention de démarrage pour chercheurs en début de carrière |
Li |
Chercheur principal |
Bowen Li |
350,000.00 |
Nonviral Delivery of Prime Editors for Gene Therapy of Cystic Fibrosis |
Troubles pulmonaires |
Thérapie génique, Administration génique non virale, nanoparticules lipidiques, édition génique, administration d’ARNm, prime editing |
Cystic fibrosis (CF) is a life-threatening genetic disease affecting over 4,500 Canadians and 95,000 people globally, caused by mutations in the CFTR gene. For patients with nonsense mutations like G542X, current treatments are ineffective, leaving a critical unmet need. This project aims to develop an inhalable gene-editing therapy using prime editors (PEs) to precisely correct the G542X mutation. These advanced genome-editing tools will be delivered directly to the lungs via lipid nanoparticles (LNPs), which are engineered to overcome barriers like thick mucus and ensure efficient delivery to lung cells._x000D_
The therapy will be tested in CF patient-derived cells and animal models, with key deliverables including a library of optimized LNPs and a validated PE system capable of restoring CFTR function. By combining cutting-edge gene-editing technology with an innovative non-viral delivery platform, this project exemplifies Canadian research excellence and innovation._x000D_
The anticipated health benefits include improved outcomes and quality of life for CF patients, particularly those without effective treatments. The adaptable LNP platform also holds potential for treating other genetic diseases, positioning Canada as a Chercheur principaler in regenerative medicine. This work could reduce long-term healthcare costs and drive economic growth through biotechnological innovation and new therapeutic developments, delivering significant social and economic benefits for Canadians. |
01/01/1970 |
31/03/2028 |
| 2025 |
Tara MacDonald (P) |
University of Toronto |
Subvention de démarrage pour chercheurs en début de carrière |
MacDonald |
Chercheuse principale |
Tara MacDonald |
349,920.00 |
Finetuning metabolic pathways to optimize stem cell-derived islet function in vitro and in vivo |
Diabète |
Îlots issus de cellules souches, métabolisme cellulaire, Diabète de type 1 (DT1), in vitro, thérapie cellulaire |
Type 1 Diabetes (T1D) is a devastating disease that affects 8 million people globally, who each require daily insulin injections to manage their blood glucose. Autoimmunity destroys insulin-producing beta cells that are housed within pancreatic islets. For people with T1D insulin is life-saving, but is not a true cure, since serious complications and large fluctuations in their blood sugars remain challenging. Over the past 10 years, scientists have developed protocols to generate insulin-producing beta cells, known as stem-cell islets (sc-islets) from human pluripotent stem cells (hPSCs). This type of cell therapy is immensely promising for curing T1D. However, beta cells within sc-islets are not perfectly functional. They do not behave exactly like islets from adult humans. Part of our research is dedicated to studying the glitches that develop in sc-islet functions. One key feature is that cell metabolism and glucose processing are abnormal in sc-islets. Our short-term goal is to use molecular biology, engineering, biochemistry and physiology to study sc-islets, so that we can design strategies in lab to "rescue" their functions. We will then test whether these islets with boosted function can improve blood glucose in mice with T1D. We are collaborating with a team of Chercheur principaling experts at the University of Toronto -- where insulin was discovered -- as we seek to help create a better cell therapy product for Canadians living with T1D. |
01/01/1970 |
31/03/2028 |
| 2025 |
Stephan Ong Tone (P) |
Sunnybrook Research Institute |
Subvention de démarrage pour chercheurs en début de carrière |
Ong Tone |
Chercheur principal |
Stephan Ong Tone |
350,000.00 |
Investigating the innate regenerative potential of the corneal endothelium as a treatment for Fuchs dystrophy |
Maladies oculaires |
Cornée, œil, cellules progénitrices, séquençage d’ARN, thérapie génique, stress oxydatif |
The cornea is the transparent front part of the eye that allows us to see, and damage to it results in decreased vision and eye pain. Corneal disease is a Chercheur principaling cause of blindness worldwide and affects many Canadians. The corneal endothelium is the inner layer of the cornea that plays a key role in keeping the cornea clear. Fuchs endothelial corneal dystrophy (FECD) is the most common disease of the corneal endothelium and is the Chercheur principaling indication for corneal transplantation worldwide. For some patients with FECD, corneal transplantation is an option, but approximately 53% of the world’s population does not have access. There is thus a significant need to better understand FECD so that new treatments can be developed. My unique position as a clinician-scientist and corneal surgeon in Canada allows me to identify gaps in clinical care and develop strategies to close these gaps. Our research aims to understand why FECD occurs by studying the characteristics of different corneal endothelial cells from FECD patients and developing therapeutics targeting corneal regeneration. We have identified novel therapeutics that protect the cornea from oxidative stress and cell death that occurs in FECD, and stimulate corneal regeneration. Our research will be a valuable resource for the research community and will highlight Canadian research excellence and innovation. We strive that our therapeutics can positively impact the health of individuals living with vision loss. |
01/01/1970 |
31/03/2028 |
| 2025 |
Michael Laflamme (C) |
University Health Network |
Subvention de démarrage pour chercheurs en début de carrière |
Protze |
Cochercheuse |
Michael Laflamme, Robert Hamilton, Stephanie Protze |
27,508.00 |
Developing a stem cell-based conduction bridge for patients with atrioventricular block |
Troubles cardiaques |
Pont de conduction biologique, cellules souches pluripotentes humaines, cellules du nœud atrio-ventriculaire, bloc AV, bloc cardiaque, nœud auriculo-ventriculaire, stimulateur cardiaque |
Each contraction of the bottom chambers of the heart is initiated by specialized atrioventricular node (AVN) pacemaker cells. Damage to these cells results in a condition called heart-block, with life-threatening slow heart rates. The best treatment currently available is the implantation of an electronic pacemaker (EPM). Approximately 15,000 Canadians receive an EPM due to heart-block every year. EPMs are associated with complications including the risk to develop heart failure and require recurrent surgical battery replacements, especially affecting pediatric patients. A biological conduction bridge (BioCB) consisting of AVN pacemaker cells that could replace the damaged AVN cells and bridge the heart-block could overcome these issues. _x000D_
This project will establish protocols to generate AVN-like pacemaker cells (AVNLPCs) from stem cells that closely match the AVN pacemaker cells in the human heart. In addition, we will provide first proof of concept that these AVNLPCs can function as a BioCB when transplanted in an animal model of heart-block. To the best of our knowledge this innovative approach has not yet been explored by any other research team. Taken together, this research will initiate translation of the BioCB towards the clinic and has the potential to provide an improved and potentially curative therapy for patients with heart-block in Canada and worldwide. |
01/01/1970 |
31/03/2028 |
| 2025 |
Robert Hamilton (C) |
The Hospital for Sick Children |
Subvention de démarrage pour chercheurs en début de carrière |
Protze |
Cochercheuse |
Michael Laflamme, Robert Hamilton, Stephanie Protze |
15,252.00 |
Developing a stem cell-based conduction bridge for patients with atrioventricular block |
Troubles cardiaques |
Pont de conduction biologique, cellules souches pluripotentes humaines, cellules du nœud atrio-ventriculaire, bloc AV, bloc cardiaque, nœud auriculo-ventriculaire, stimulateur cardiaque |
Each contraction of the bottom chambers of the heart is initiated by specialized atrioventricular node (AVN) pacemaker cells. Damage to these cells results in a condition called heart-block, with life-threatening slow heart rates. The best treatment currently available is the implantation of an electronic pacemaker (EPM). Approximately 15,000 Canadians receive an EPM due to heart-block every year. EPMs are associated with complications including the risk to develop heart failure and require recurrent surgical battery replacements, especially affecting pediatric patients. A biological conduction bridge (BioCB) consisting of AVN pacemaker cells that could replace the damaged AVN cells and bridge the heart-block could overcome these issues. _x000D_
This project will establish protocols to generate AVN-like pacemaker cells (AVNLPCs) from stem cells that closely match the AVN pacemaker cells in the human heart. In addition, we will provide first proof of concept that these AVNLPCs can function as a BioCB when transplanted in an animal model of heart-block. To the best of our knowledge this innovative approach has not yet been explored by any other research team. Taken together, this research will initiate translation of the BioCB towards the clinic and has the potential to provide an improved and potentially curative therapy for patients with heart-block in Canada and worldwide. |
01/01/1970 |
31/03/2028 |
| 2025 |
Stephanie Protze (P) |
University Health Network |
Subvention de démarrage pour chercheurs en début de carrière |
Protze |
Chercheuse principale |
Michael Laflamme, Robert Hamilton, Stephanie Protze |
306,861.00 |
Developing a stem cell-based conduction bridge for patients with atrioventricular block |
Troubles cardiaques |
Pont de conduction biologique, cellules souches pluripotentes humaines, cellules du nœud atrio-ventriculaire, bloc AV, bloc cardiaque, nœud auriculo-ventriculaire, stimulateur cardiaque |
Each contraction of the bottom chambers of the heart is initiated by specialized atrioventricular node (AVN) pacemaker cells. Damage to these cells results in a condition called heart-block, with life-threatening slow heart rates. The best treatment currently available is the implantation of an electronic pacemaker (EPM). Approximately 15,000 Canadians receive an EPM due to heart-block every year. EPMs are associated with complications including the risk to develop heart failure and require recurrent surgical battery replacements, especially affecting pediatric patients. A biological conduction bridge (BioCB) consisting of AVN pacemaker cells that could replace the damaged AVN cells and bridge the heart-block could overcome these issues. _x000D_
This project will establish protocols to generate AVN-like pacemaker cells (AVNLPCs) from stem cells that closely match the AVN pacemaker cells in the human heart. In addition, we will provide first proof of concept that these AVNLPCs can function as a BioCB when transplanted in an animal model of heart-block. To the best of our knowledge this innovative approach has not yet been explored by any other research team. Taken together, this research will initiate translation of the BioCB towards the clinic and has the potential to provide an improved and potentially curative therapy for patients with heart-block in Canada and worldwide. |
01/01/1970 |
31/03/2028 |
| 2025 |
Gregor Andelfinger (C) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de démarrage pour chercheurs en début de carrière |
Savoji |
Cochercheur |
Gregor Andelfinger, Houman Savoji |
45,000.00 |
From Stem Cells to Function: 3D Bioprinted Living Pulmonary Valves for Pediatric Patients |
Troubles cardiaques |
Cellules souches pluripotentes humaines, valves cardiaques, bio-impression 3D, ingénierie tissulaire, fonction biomécanique, patients pédiatriques, maladies valvulaires congénitales |
Congenital heart diseases (CHDs) are a major cause of health challenges in children, often requiring the replacement of the pulmonary valve in the heart. Unfortunately, current artificial heart valves cannot grow with the child, forcing many pediatric patients to undergo multiple surgeries as they age. These repeated surgeries not only pose serious health risks but also greatly reduce the quality of life for affected children and place a heavy financial burden on healthcare systems._x000D_
_x000D_
Our project aims to address these challenges by creating innovative, patient-specific heart valves using cutting-edge stem cells and 3D bioprinting technologies. These valves will be made from living cells and are designed to grow and adapt to the child’s heart, potentially eliminating the need for multiple surgeries. We will achieve this by combining insights from stem cell biology, developmental biology, advanced imaging, bioprinting, and specialized lab techniques to design and test these innovative valves._x000D_
_x000D_
If successful, this research will revolutionize treatment for children with CHDs by providing safer, more effective, and cost-efficient solutions. It represents a breakthrough in pediatric medicine, with the potential to improve lives, reduce healthcare costs, and set a new standard for personalized care in regenerative medicine. |
01/01/1970 |
31/03/2028 |
| 2025 |
Houman Savoji (P) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de démarrage pour chercheurs en début de carrière |
Savoji |
Chercheur principal |
Gregor Andelfinger, Houman Savoji |
305,000.00 |
From Stem Cells to Function: 3D Bioprinted Living Pulmonary Valves for Pediatric Patients |
Troubles cardiaques |
Cellules souches pluripotentes humaines, valves cardiaques, bio-impression 3D, ingénierie tissulaire, fonction biomécanique, patients pédiatriques, maladies valvulaires congénitales |
Congenital heart diseases (CHDs) are a major cause of health challenges in children, often requiring the replacement of the pulmonary valve in the heart. Unfortunately, current artificial heart valves cannot grow with the child, forcing many pediatric patients to undergo multiple surgeries as they age. These repeated surgeries not only pose serious health risks but also greatly reduce the quality of life for affected children and place a heavy financial burden on healthcare systems._x000D_
_x000D_
Our project aims to address these challenges by creating innovative, patient-specific heart valves using cutting-edge stem cells and 3D bioprinting technologies. These valves will be made from living cells and are designed to grow and adapt to the child’s heart, potentially eliminating the need for multiple surgeries. We will achieve this by combining insights from stem cell biology, developmental biology, advanced imaging, bioprinting, and specialized lab techniques to design and test these innovative valves._x000D_
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If successful, this research will revolutionize treatment for children with CHDs by providing safer, more effective, and cost-efficient solutions. It represents a breakthrough in pediatric medicine, with the potential to improve lives, reduce healthcare costs, and set a new standard for personalized care in regenerative medicine. |
01/01/1970 |
31/03/2028 |
| 2025 |
Carl de Boer (C) |
University of British Columbia |
Subvention de démarrage pour chercheurs en début de carrière |
Shakiba |
Cochercheuse |
Carl de Boer, Nika Shakiba |
52,500.00 |
Expanding the quality control toolbox: a machine-learning approach to detecting genetically aberrant pluripotent stem cells |
Multiples maladies |
Cellules souches pluripotentes, mutations génétiques, apprentissage machine, biologie des systèmes, bioingénierie des cellules souches, expansion cellulaire |
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to detect signatures of variants in hPSC culture. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at each cell and untangle these complex datasets using machine learning. Concurrently, we will provide mechanistic insights into the potential for variants to survive in hPSC-derived cell products. Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world Chercheur principaler in cell therapy manufacturing for regenerative medicine. |
01/01/1970 |
31/03/2028 |
| 2025 |
Nika Shakiba (P) |
University of British Columbia |
Subvention de démarrage pour chercheurs en début de carrière |
Shakiba |
Chercheuse principale |
Carl de Boer, Nika Shakiba |
297,500.00 |
Expanding the quality control toolbox: a machine-learning approach to detecting genetically aberrant pluripotent stem cells |
Multiples maladies |
Cellules souches pluripotentes, mutations génétiques, apprentissage machine, biologie des systèmes, bioingénierie des cellules souches, expansion cellulaire |
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to detect signatures of variants in hPSC culture. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at each cell and untangle these complex datasets using machine learning. Concurrently, we will provide mechanistic insights into the potential for variants to survive in hPSC-derived cell products. Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world Chercheur principaler in cell therapy manufacturing for regenerative medicine. |
01/01/1970 |
31/03/2028 |
| 2025 |
Marie-Claude Sincennes (P) |
Institut national de la recherche scientifique (INRS) |
Subvention de démarrage pour chercheurs en début de carrière |
Sincennes |
Chercheuse principale |
Marie-Claude Sincennes, Nicolas Dumont |
263,200.00 |
Role of PABPN1 in muscle stem and progenitor cells to understand oculopharyngeal muscular dystrophy |
Troubles musculo-squelettiques |
Dystrophie musculaire oculopharyngée, PABPN1, protéine de liaison de l’ARN, cellules souches musculaires, régénération musculaire, transcriptomique |
Oculopharyngeal muscular dystrophy (OPMD) is a neuromuscular disorder that is more frequent in the province of Quebec compared to the rest of the world. OPMD affects voluntary muscles (face, eyelids, throat and limbs), develops slowly and may eventually Chercheur principal to the use of a wheelchair. It is caused by mutations in the PABPN1 gene, which regulates gene expression. However, it is not clear how the mutation of PABPN1 perturbs normal muscle function and contributes to the development of OPMD. Our research project aims at deciphering what is the function of PABPN1 in muscle stem and progenitor cells, two cell types that are likely involved in OPMD progression. This project will improve our understanding of the molecular mechanisms that are altered in OPMD, a prerequisite for the development of therapeutic strategies. |
01/01/1970 |
31/03/2028 |
| 2025 |
Nicolas Dumont (C) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de démarrage pour chercheurs en début de carrière |
Sincennes |
Cochercheuse |
Marie-Claude Sincennes, Nicolas Dumont |
86,800.00 |
Role of PABPN1 in muscle stem and progenitor cells to understand oculopharyngeal muscular dystrophy |
Troubles musculo-squelettiques |
Dystrophie musculaire oculopharyngée, PABPN1, protéine de liaison de l’ARN, cellules souches musculaires, régénération musculaire, transcriptomique |
Oculopharyngeal muscular dystrophy (OPMD) is a neuromuscular disorder that is more frequent in the province of Quebec compared to the rest of the world. OPMD affects voluntary muscles (face, eyelids, throat and limbs), develops slowly and may eventually Chercheur principal to the use of a wheelchair. It is caused by mutations in the PABPN1 gene, which regulates gene expression. However, it is not clear how the mutation of PABPN1 perturbs normal muscle function and contributes to the development of OPMD. Our research project aims at deciphering what is the function of PABPN1 in muscle stem and progenitor cells, two cell types that are likely involved in OPMD progression. This project will improve our understanding of the molecular mechanisms that are altered in OPMD, a prerequisite for the development of therapeutic strategies. |
01/01/1970 |
31/03/2028 |
| 2025 |
Anastassia Voronova (P) |
University of Alberta |
Subvention de démarrage pour chercheurs en début de carrière |
Voronova |
Chercheuse principale |
Anastassia Voronova, Ayman El-Kadi, Frederick West, Khaled Barakat |
276,000.00 |
CX3CR1 agonists for neurodegeneration |
Maladies et troupes du système nerveux central (SNC) |
Remyélinisation, régénération, OPC, oligodendrocyte, cuprizone |
Myelin is a fatty substance that coats nerve projections for efficient signal propagation. When myelin is damaged, demyelination disorders occur Chercheur principaling to neurological impairments in vision, movement and/or cognition. Demyelination occurs in multiple sclerosis (MS), which is caused by abnormal activity of the immune system whereby the body’s own immune cells damage myelin and myelin-producing cells, oligodendrocytes, in the central nervous system (brain and spinal cord). Current MS treatments target inflammation and aid patients with relapse-remitting MS, in which episodes of neurological dysfunction are followed by remission. Yet, they are ineffective for progressive MS, which usually evolves from the relapsing stage and involves a continual worsening of the disease with no improvement. Effective treatments for this type of MS would require remyelination (restoration of myelin). Remyelination can be achieved by forming new oligodendrocytes from oligodendrocyte precursor cells in the human central nervous system. However, this process is highly inefficient in MS patients. We have discovered that fractalkine (CX3CL1), a naturally occurring molecule in the brain, increases remyelination by activating fractalkine receptor (CX3CR1) present on oligodendrocyte precursor cells. This effect could form the basis of much needed future MS therapies. This proposal will address the exciting possibility of remyelination therapies in MS using the candidate brain penetrant CX3CR1 agonists. |
01/01/1970 |
31/03/2028 |
| 2025 |
Ayman El-Kadi (C) |
University of Alberta |
Subvention de démarrage pour chercheurs en début de carrière |
Voronova |
Cochercheuse |
Anastassia Voronova, Ayman El-Kadi, Frederick West, Khaled Barakat |
10,000.00 |
CX3CR1 agonists for neurodegeneration |
Maladies et troupes du système nerveux central (SNC) |
Remyélinisation, régénération, OPC, oligodendrocyte, cuprizone |
Myelin is a fatty substance that coats nerve projections for efficient signal propagation. When myelin is damaged, demyelination disorders occur Chercheur principaling to neurological impairments in vision, movement and/or cognition. Demyelination occurs in multiple sclerosis (MS), which is caused by abnormal activity of the immune system whereby the body’s own immune cells damage myelin and myelin-producing cells, oligodendrocytes, in the central nervous system (brain and spinal cord). Current MS treatments target inflammation and aid patients with relapse-remitting MS, in which episodes of neurological dysfunction are followed by remission. Yet, they are ineffective for progressive MS, which usually evolves from the relapsing stage and involves a continual worsening of the disease with no improvement. Effective treatments for this type of MS would require remyelination (restoration of myelin). Remyelination can be achieved by forming new oligodendrocytes from oligodendrocyte precursor cells in the human central nervous system. However, this process is highly inefficient in MS patients. We have discovered that fractalkine (CX3CL1), a naturally occurring molecule in the brain, increases remyelination by activating fractalkine receptor (CX3CR1) present on oligodendrocyte precursor cells. This effect could form the basis of much needed future MS therapies. This proposal will address the exciting possibility of remyelination therapies in MS using the candidate brain penetrant CX3CR1 agonists. |
01/01/1970 |
31/03/2028 |
| 2025 |
Frederick West (C) |
University of Alberta |
Subvention de démarrage pour chercheurs en début de carrière |
Voronova |
Cochercheuse |
Anastassia Voronova, Ayman El-Kadi, Frederick West, Khaled Barakat |
50,000.00 |
CX3CR1 agonists for neurodegeneration |
Maladies et troupes du système nerveux central (SNC) |
Remyélinisation, régénération, OPC, oligodendrocyte, cuprizone |
Myelin is a fatty substance that coats nerve projections for efficient signal propagation. When myelin is damaged, demyelination disorders occur Chercheur principaling to neurological impairments in vision, movement and/or cognition. Demyelination occurs in multiple sclerosis (MS), which is caused by abnormal activity of the immune system whereby the body’s own immune cells damage myelin and myelin-producing cells, oligodendrocytes, in the central nervous system (brain and spinal cord). Current MS treatments target inflammation and aid patients with relapse-remitting MS, in which episodes of neurological dysfunction are followed by remission. Yet, they are ineffective for progressive MS, which usually evolves from the relapsing stage and involves a continual worsening of the disease with no improvement. Effective treatments for this type of MS would require remyelination (restoration of myelin). Remyelination can be achieved by forming new oligodendrocytes from oligodendrocyte precursor cells in the human central nervous system. However, this process is highly inefficient in MS patients. We have discovered that fractalkine (CX3CL1), a naturally occurring molecule in the brain, increases remyelination by activating fractalkine receptor (CX3CR1) present on oligodendrocyte precursor cells. This effect could form the basis of much needed future MS therapies. This proposal will address the exciting possibility of remyelination therapies in MS using the candidate brain penetrant CX3CR1 agonists. |
01/01/1970 |
31/03/2028 |
| 2025 |
Khaled Barakat (C) |
University of Alberta |
Subvention de démarrage pour chercheurs en début de carrière |
Voronova |
Cochercheuse |
Anastassia Voronova, Ayman El-Kadi, Frederick West, Khaled Barakat |
14,000.00 |
CX3CR1 agonists for neurodegeneration |
Maladies et troupes du système nerveux central (SNC) |
Remyélinisation, régénération, OPC, oligodendrocyte, cuprizone |
Myelin is a fatty substance that coats nerve projections for efficient signal propagation. When myelin is damaged, demyelination disorders occur Chercheur principaling to neurological impairments in vision, movement and/or cognition. Demyelination occurs in multiple sclerosis (MS), which is caused by abnormal activity of the immune system whereby the body’s own immune cells damage myelin and myelin-producing cells, oligodendrocytes, in the central nervous system (brain and spinal cord). Current MS treatments target inflammation and aid patients with relapse-remitting MS, in which episodes of neurological dysfunction are followed by remission. Yet, they are ineffective for progressive MS, which usually evolves from the relapsing stage and involves a continual worsening of the disease with no improvement. Effective treatments for this type of MS would require remyelination (restoration of myelin). Remyelination can be achieved by forming new oligodendrocytes from oligodendrocyte precursor cells in the human central nervous system. However, this process is highly inefficient in MS patients. We have discovered that fractalkine (CX3CL1), a naturally occurring molecule in the brain, increases remyelination by activating fractalkine receptor (CX3CR1) present on oligodendrocyte precursor cells. This effect could form the basis of much needed future MS therapies. This proposal will address the exciting possibility of remyelination therapies in MS using the candidate brain penetrant CX3CR1 agonists. |
01/01/1970 |
31/03/2028 |
| 2025 |
Anthony Flamier (P) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de démarrage pour chercheurs en début de carrière (cofinancée par la Fondation Azrieli) |
Flamier |
Chercheur principal |
Anthony Flamier |
210,000.00 |
Regenerative Approaches to Rett Syndrome by Targeting Primary Cilia Dysfunction. |
Maladies et troupes du système nerveux central (SNC) |
Syndrome de Rett, SCPi, Cils, neurodéveloppement, modélisation des maladies, organoïdes cérébraux, CRISPR |
This regenerative medicine project addresses Rett syndrome (RTT), a severe neurological disorder caused by MECP2 mutations that primarily affects young girls, Chercheur principaling to significant cognitive and physical disabilities. By focusing on primary cilia dysfunction—an underexplored aspect of RTT pathology—we aim to uncover novel therapeutic avenues. Using neurons and brain organoids derived from RTT patient-specific induced pluripotent stem cells (iPSCs), we will investigate structural and functional abnormalities in primary cilia, validating our findings with post-mortem brain tissues. Concurrently, we will screen FDA-approved drugs to identify candidates that restore cilia function and neuronal activity, leveraging advanced imaging and electrophysiology to assess therapeutic potential. This project exemplifies Canadian innovation by addressing a critical unmet need in RTT, with the potential to accelerate treatment development, improve the quality of life for patients, and reinforce Canada’s Chercheur principalership in regenerative medicine and neuroscience. |
01/01/1970 |
31/03/2028 |
| 2025 |
Craig Simmons (P) |
University of Toronto |
Subvention de soutien aux partenariats biotechnologiques |
Simmons |
Chercheur principal |
Craig Simmons, Julie Audet, Michael Laflamme, Milica Radisic |
325,000.00 |
Algorithm-directed optimization of defined media to mature iPSC-derived cardiac organoids for cell therapy |
Troubles cardiaques |
Thérapie cellulaire cardiaque, cellules souches pluripotentes induites, milieu, optimisation, maturation |
Repairing damaged heart muscle with transplanted human stem cell-derived heart cells (hPSC-CMs) shows promise for improving heart function. However, challenges remain: the cells integrate poorly and can cause irregular heart rhythms. Research suggests that maturing these cells in the lab improves their effectiveness, but current methods only produce immature, neonatal-like cells, limiting their therapeutic potential._x000D_
_x000D_
Our team, led by Dr. Simmons, has developed a breakthrough cell culture medium that promotes the maturation of hPSC-CMs. Using a computational tool, we optimized 17 ingredients to create a formula that outperforms existing options. This medium is already licensed for research applications._x000D_
_x000D_
Now, we aim to create an advanced medium specifically for cardiac cell therapy. Partnering with BoutIQ Solutions, we will use their machine-learning algorithm, HiDiNeu, to optimize 24 ingredients more efficiently. The best formulations will be tested in collaboration with experts in lab automation and guinea pig heart models to identify formulations most suited for cell therapy._x000D_
_x000D_
This project will deliver new media to improve cardiac treatments and computational tools to accelerate stem cell research. Intellectual property will be licensed by BoutIQ for commercialization, advancing innovative heart disease therapies. |
01/01/1970 |
31/03/2027 |
| 2025 |
Julie Audet (C) |
University of Toronto |
Subvention de soutien aux partenariats biotechnologiques |
Simmons |
Cochercheur |
Craig Simmons, Julie Audet, Michael Laflamme, Milica Radisic |
46,000.00 |
Algorithm-directed optimization of defined media to mature iPSC-derived cardiac organoids for cell therapy |
Troubles cardiaques |
Thérapie cellulaire cardiaque, cellules souches pluripotentes induites, milieu, optimisation, maturation |
Repairing damaged heart muscle with transplanted human stem cell-derived heart cells (hPSC-CMs) shows promise for improving heart function. However, challenges remain: the cells integrate poorly and can cause irregular heart rhythms. Research suggests that maturing these cells in the lab improves their effectiveness, but current methods only produce immature, neonatal-like cells, limiting their therapeutic potential._x000D_
_x000D_
Our team, led by Dr. Simmons, has developed a breakthrough cell culture medium that promotes the maturation of hPSC-CMs. Using a computational tool, we optimized 17 ingredients to create a formula that outperforms existing options. This medium is already licensed for research applications._x000D_
_x000D_
Now, we aim to create an advanced medium specifically for cardiac cell therapy. Partnering with BoutIQ Solutions, we will use their machine-learning algorithm, HiDiNeu, to optimize 24 ingredients more efficiently. The best formulations will be tested in collaboration with experts in lab automation and guinea pig heart models to identify formulations most suited for cell therapy._x000D_
_x000D_
This project will deliver new media to improve cardiac treatments and computational tools to accelerate stem cell research. Intellectual property will be licensed by BoutIQ for commercialization, advancing innovative heart disease therapies. |
01/01/1970 |
31/03/2027 |
| 2025 |
Michael Laflamme (C) |
University Health Network |
Subvention de soutien aux partenariats biotechnologiques |
Simmons |
Cochercheur |
Craig Simmons, Julie Audet, Michael Laflamme, Milica Radisic |
30,000.00 |
Algorithm-directed optimization of defined media to mature iPSC-derived cardiac organoids for cell therapy |
Troubles cardiaques |
Thérapie cellulaire cardiaque, cellules souches pluripotentes induites, milieu, optimisation, maturation |
Repairing damaged heart muscle with transplanted human stem cell-derived heart cells (hPSC-CMs) shows promise for improving heart function. However, challenges remain: the cells integrate poorly and can cause irregular heart rhythms. Research suggests that maturing these cells in the lab improves their effectiveness, but current methods only produce immature, neonatal-like cells, limiting their therapeutic potential._x000D_
_x000D_
Our team, led by Dr. Simmons, has developed a breakthrough cell culture medium that promotes the maturation of hPSC-CMs. Using a computational tool, we optimized 17 ingredients to create a formula that outperforms existing options. This medium is already licensed for research applications._x000D_
_x000D_
Now, we aim to create an advanced medium specifically for cardiac cell therapy. Partnering with BoutIQ Solutions, we will use their machine-learning algorithm, HiDiNeu, to optimize 24 ingredients more efficiently. The best formulations will be tested in collaboration with experts in lab automation and guinea pig heart models to identify formulations most suited for cell therapy._x000D_
_x000D_
This project will deliver new media to improve cardiac treatments and computational tools to accelerate stem cell research. Intellectual property will be licensed by BoutIQ for commercialization, advancing innovative heart disease therapies. |
01/01/1970 |
31/03/2027 |
| 2025 |
Milica Radisic (C) |
University Health Network |
Subvention de soutien aux partenariats biotechnologiques |
Simmons |
Cochercheur |
Craig Simmons, Julie Audet, Michael Laflamme, Milica Radisic |
20,000.00 |
Algorithm-directed optimization of defined media to mature iPSC-derived cardiac organoids for cell therapy |
Troubles cardiaques |
Thérapie cellulaire cardiaque, cellules souches pluripotentes induites, milieu, optimisation, maturation |
Repairing damaged heart muscle with transplanted human stem cell-derived heart cells (hPSC-CMs) shows promise for improving heart function. However, challenges remain: the cells integrate poorly and can cause irregular heart rhythms. Research suggests that maturing these cells in the lab improves their effectiveness, but current methods only produce immature, neonatal-like cells, limiting their therapeutic potential._x000D_
_x000D_
Our team, led by Dr. Simmons, has developed a breakthrough cell culture medium that promotes the maturation of hPSC-CMs. Using a computational tool, we optimized 17 ingredients to create a formula that outperforms existing options. This medium is already licensed for research applications._x000D_
_x000D_
Now, we aim to create an advanced medium specifically for cardiac cell therapy. Partnering with BoutIQ Solutions, we will use their machine-learning algorithm, HiDiNeu, to optimize 24 ingredients more efficiently. The best formulations will be tested in collaboration with experts in lab automation and guinea pig heart models to identify formulations most suited for cell therapy._x000D_
_x000D_
This project will deliver new media to improve cardiac treatments and computational tools to accelerate stem cell research. Intellectual property will be licensed by BoutIQ for commercialization, advancing innovative heart disease therapies. |
01/01/1970 |
31/03/2027 |
| 2025 |
Amy Wong (P) |
The Hospital for Sick Children |
Subvention de soutien aux partenariats biotechnologiques |
Wong |
Chercheuse principale |
Amy Wong, Bowen Li |
336,200.00 |
Dualase Gene Therapy for Cystic Fibrosis Lung Disease |
Troubles pulmonaires |
Cellules souches pluripotentes induites, fibrose kystique, thérapie génique, CRISPR-Cas9, édition génique, nanoparticules lipidiques, souris humanisée |
The total number of individuals with cystic fibrosis (CF) in Canada is estimated to be around 4,500. In 2021, the total socioeconomic burden of CF in Canada was $414 million, with two-thirds of the cost attributed to direct expenses, such as medications. Trikafta™, a new combination drug, is currently used to treat individuals with the most common CF mutation, F508del, offering therapy to approximately 90% of those with CF. However, real-time data indicates that not all individuals have benefited from Trikafta, and those with rare CF variants (10% of the global CF population) are not eligible for the drug, as it is not expected to be effective for them. Additionally, the drugs, taken daily, are costly ($300,000 per year), and the long-term health effects are still unknown._x000D_
_x000D_
Our proposal seeks to test the efficacy of a lung-specific lipid nanoparticle (LNP) delivery system to administer our novel gene editor, “Dualase,” in stem cell-derived airway cells and in mouse models that carry human CFTR variants in their lungs. While our goal is to develop a gene therapy approach to cure CF in the airways, the broader implications of our work extend to other lung diseases, including lung cancer, surfactant deficiencies, and primary ciliary dyskinesia. |
01/01/1970 |
31/03/2027 |
| 2025 |
Bowen Li (C) |
University of Toronto |
Subvention de soutien aux partenariats biotechnologiques |
Wong |
Cochercheuse |
Amy Wong, Bowen Li |
93,800.00 |
Dualase Gene Therapy for Cystic Fibrosis Lung Disease |
Troubles pulmonaires |
Cellules souches pluripotentes induites, fibrose kystique, thérapie génique, CRISPR-Cas9, édition génique, nanoparticules lipidiques, souris humanisée |
The total number of individuals with cystic fibrosis (CF) in Canada is estimated to be around 4,500. In 2021, the total socioeconomic burden of CF in Canada was $414 million, with two-thirds of the cost attributed to direct expenses, such as medications. Trikafta™, a new combination drug, is currently used to treat individuals with the most common CF mutation, F508del, offering therapy to approximately 90% of those with CF. However, real-time data indicates that not all individuals have benefited from Trikafta, and those with rare CF variants (10% of the global CF population) are not eligible for the drug, as it is not expected to be effective for them. Additionally, the drugs, taken daily, are costly ($300,000 per year), and the long-term health effects are still unknown._x000D_
_x000D_
Our proposal seeks to test the efficacy of a lung-specific lipid nanoparticle (LNP) delivery system to administer our novel gene editor, “Dualase,” in stem cell-derived airway cells and in mouse models that carry human CFTR variants in their lungs. While our goal is to develop a gene therapy approach to cure CF in the airways, the broader implications of our work extend to other lung diseases, including lung cancer, surfactant deficiencies, and primary ciliary dyskinesia. |
01/01/1970 |
31/03/2027 |
| 2025 |
Massimiliano Paganelli (P) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de soutien aux partenariats biotechnologiques (cofinancée par le CQDM) |
Paganelli |
Chercheur principal |
Massimiliano Paganelli |
200,000.00 |
Treating acute decompensation of urea cycle disorders by transient implantation of an Encapsulated Liver Tissue |
Troubles hépatiques |
Thérapie cellulaire, ingénierie tissulaire, SCPi, maladies hépatiques, troubles du cycle de l’urée |
Children with urea cycle disorders (UCD) face life-threatening crises caused by their bodies’ inability to eliminate ammonia. These crises can Chercheur principal to severe brain damage or death if untreated. Current treatments are insufficient, and liver transplantation, the only curative option, becomes often available only once irreversible neurological damage is already done. Gene therapy is being developed and holds promise for a cure but cannot yet address early-life crises. There is a critical need for a fast and effective treatment for these crises that might bridge newborns and young children safely to curative options like gene therapy or liver transplantation. Our project aims to address this gap by repurposing an innovative regenerative medicine product called Encapsulated Liver Tissue (ELT). The ELT, derived from stem cells, mimics liver function and can rapidly reduce ammonia levels without requiring immunosuppression. This product has already shown success in treating liver failure in preclinical studies and is on track for clinical trials in 2026. In this study, we will evaluate the ELT’s effectiveness in managing UCD-related hyperammonemia. First, we will test its ammonia-clearing capacity in the lab, followed by trials in animal models of UCD to assess its safety and ability to prevent brain damage. If successful, this project could bring a transformative treatment to children with UCD, providing them a chance to survive and safely reach curative therapies. |
01/01/1970 |
31/03/2027 |
| 2025 |
Timothy Kieffer (P) |
University of British Columbia |
Subvention de soutien aux partenariats biotechnologiques (cofinancée par le CQDM) |
Kieffer |
Chercheur principal |
Timothy Kieffer |
258,000.00 |
Vascularized, Stem Cell-Derived Islet Organoids for the Treatment of Type 1 Diabetes |
Diabète |
Organoïdes d’îlots pancréatiques, thérapie cellulaire, diabète de type 1, insuline, cellules souches pluripotentes, prévascularisation, site sous-cutané |
Diabetes is a disease in which patients’ immune systems attack their own insulin-producing beta cells. Without insulin, patients’ blood sugar levels are not effectively controlled in response to meals and other factors. Current treatments require patients to monitor their own blood sugar and deliver insulin as needed. These treatments are mentally taxing and Chercheur principal to ineffective blood glucose control, predisposing patients to long-term complications._x000D_
_x000D_
Cell therapies, in which beta cells from either deceased donors or pluripotent stem cells are transplanted into patients living with diabetes, can effectively control blood sugar levels. Such therapies remove the burden of disease management and can prevent long-term health complications. However, these treatments are limited by low graft cell survival and therefore require that large numbers of cells be used for treatment, causing logistical and manufacturing issues. Even with high numbers of transplanted cells, graft survival declines over time, with patients often forced to return to exogenous insulin._x000D_
_x000D_
Lunar Therapeutics and the academic team of collaborators seek to increase cell survival to maximize the impact of cell therapies for diabetes. By producing stem cell-derived islet organoids that are pre-primed for vascularization, and transplanting them using a minimally invasive technique, the team will improve cell survival and function, thus alleviating the disease burden and long-term health risks of type 1 diabetes. |
01/01/1970 |
31/03/2027 |
| 2025 |
Christian Beausejour (P) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de soutien aux projets à fort impact |
Beausejour |
Chercheur principal |
Christian Beausejour |
270,000.00 |
Development of improved NK cell therapies for the elimination of senescent cancer cells |
Cancer |
Sénescence, immunogénicité, cellules tueuses naturelles (CTN), SCPi, souris humanisée |
As we age or undergo treatments like chemotherapy, certain cells become "senescent," meaning they stop dividing and take on an inflammatory profile. These cells can actually help cancer grow and spread. Finding ways to remove these senescent cells, or "senolytic" therapies, could improve cancer treatments. Our lab is focusing on using a type of immune cell called NK (natural killer) cells to target and destroy these harmful, senescent cells. However, senescent cells have ways of protecting themselves from being killed by NK cells. They do this by expressing certain molecules that inhibit NK cell activity. To tackle this problem, we’re working on creating NK cells that are genetically modified to get around these defense mechanisms. Specifically, we’ve made NK cells that don’t respond to the inhibitory signals from senescent cells, so they can more effectively target and kill them. We’re testing these modified NK cells in lab models to see if they can successfully eliminate senescent cells in the body. Our research has two main goals:_x000D_
_x000D_
1. Test the effectiveness of these engineered NK cells (called iNK cells) in killing senescent cancer cells._x000D_
2. Screen existing FDA-approved drugs to see if any of them can make senescent cancer cells even more vulnerable to NK cell attacks._x000D_
By completing this work, we hope to create a new form of cell therapy that could make cancer treatments more effective by removing the harmful, senescent cells that can promote cancer growth. |
01/01/1970 |
31/03/2027 |
| 2025 |
Michel Tremblay (C) |
Université McGill |
Subvention de soutien aux projets à fort impact |
Chang |
Cochercheuse |
Michel Tremblay, Natasha Chang |
30,000.00 |
Restoring muscle stem cell differentiation to enhance regeneration in muscular dystrophy |
Troubles musculo-squelettiques |
Dystrophie musculaire de Duchenne, régénération musculaire, cellules souches musculaires, myogenèse, phosphatase |
Duchenne muscular dystrophy (DMD) is a severely debilitating and fatal pediatric muscle disease that affects 1 in every 5,000 Canadian male births. With the help of corticosteroids, cardiac and respiratory medical care, DMD patients can now live up to 30 years of age, but despite intense research efforts to understand the cause and progression of the disease there is still no effective cure for DMD. Historically, DMD has been viewed as a disease affecting the integrity of muscle tissue, which Chercheur principals to repetitive weakening and damage of the muscle fibers. However, new studies have shown that muscle stem cells, which are stem cells that reside within the muscle, are also affected in DMD. DMD stem cells do not function as normal healthy muscle stem cells, often failing to fully progress through the steps required to contribute to muscle repair, and their dysfunction therefore plays a role in disease progression. Moreover, current DMD therapeutic strategies do not target muscle stem cells. Our research program aims to address their dysfunction through targeting dysregulated members of a molecular pathway known as the JAK/STAT pathway that is impacted in DMD. The findings from this research program will provide a therapeutic target to restore muscle stem cell function and enhance muscle regeneration and strength in patients with DMD. |
01/01/1970 |
31/03/2027 |
| 2025 |
Natasha Chang (P) |
Université McGill |
Subvention de soutien aux projets à fort impact |
Chang |
Chercheuse principale |
Michel Tremblay, Natasha Chang |
240,000.00 |
Restoring muscle stem cell differentiation to enhance regeneration in muscular dystrophy |
Troubles musculo-squelettiques |
Dystrophie musculaire de Duchenne, régénération musculaire, cellules souches musculaires, myogenèse, phosphatase |
Duchenne muscular dystrophy (DMD) is a severely debilitating and fatal pediatric muscle disease that affects 1 in every 5,000 Canadian male births. With the help of corticosteroids, cardiac and respiratory medical care, DMD patients can now live up to 30 years of age, but despite intense research efforts to understand the cause and progression of the disease there is still no effective cure for DMD. Historically, DMD has been viewed as a disease affecting the integrity of muscle tissue, which Chercheur principals to repetitive weakening and damage of the muscle fibers. However, new studies have shown that muscle stem cells, which are stem cells that reside within the muscle, are also affected in DMD. DMD stem cells do not function as normal healthy muscle stem cells, often failing to fully progress through the steps required to contribute to muscle repair, and their dysfunction therefore plays a role in disease progression. Moreover, current DMD therapeutic strategies do not target muscle stem cells. Our research program aims to address their dysfunction through targeting dysregulated members of a molecular pathway known as the JAK/STAT pathway that is impacted in DMD. The findings from this research program will provide a therapeutic target to restore muscle stem cell function and enhance muscle regeneration and strength in patients with DMD. |
01/01/1970 |
31/03/2027 |
| 2025 |
Jason Guertin (C) |
Université Laval |
Subvention de soutien aux projets à fort impact |
Germain |
Cochercheuse |
Jason Guertin, Julie Fradette, Lucie Germain, Ma'n Zawati, Véronique Moulin |
6,160.00 |
Toward a combined gene therapy and tissue engineering novel treatment for junctional epidermolysis bullosa |
Guérison des plaies |
Épidermolyse bulleuse jonctionnelle, ingénierie tissulaire, thérapie génique, cellules souches, vecteur rétroviral, substitut cutané |
Junctional epidermolysis bullosa (JEB) is a rare genetic disease characterized by presence of bullae at birth, lack of scarring of the lesions, and early death. It is caused by genetic changes in the LAMB3, COL17A1, LAMC2, LAMA3, integrin a6ß4 or integrin a3 genes that Chercheur principals to epidermal loss and cause the skin to blister easily. There is no established cure for JEB and the treatment is palliative, mainly with bandages to protect epithelial wounds. As a continuity of our current clinical trial on the dystrophic form of epidermolysis bullosa by using an innovative approach to treat this skin condition, we aim to regenerate a fully functional epidermis for JEB patients by gene correcting their epidermal cells in the lab and use them to produce an artificial skin substitute. For this, the normal copy of the responsible gene will be delivered in JEB cells using a safe self inactivated retrovirus. The transduced cells will be used to produce sheets of skin using the autologous self-assembly method invented in the LOEX. The functionality and the mechanical properties of the produced gene corrected skin equivalents will be assessed. Until now, we recruited one JEB patient, established a cell biobank and characterize the skin cells. In a long term, the gene corrected skin substitute will be grafted in mice to determine if it safe to trial in JEB patients by gafting on wounds. If successful, this approach would provide a therapeutic option for skin lesions of JEB patients. |
01/01/1970 |
31/03/2027 |
| 2025 |
Julie Fradette (C) |
Université Laval |
Subvention de soutien aux projets à fort impact |
Germain |
Cochercheuse |
Jason Guertin, Julie Fradette, Lucie Germain, Ma'n Zawati, Véronique Moulin |
11,000.00 |
Toward a combined gene therapy and tissue engineering novel treatment for junctional epidermolysis bullosa |
Guérison des plaies |
Épidermolyse bulleuse jonctionnelle, ingénierie tissulaire, thérapie génique, cellules souches, vecteur rétroviral, substitut cutané |
Junctional epidermolysis bullosa (JEB) is a rare genetic disease characterized by presence of bullae at birth, lack of scarring of the lesions, and early death. It is caused by genetic changes in the LAMB3, COL17A1, LAMC2, LAMA3, integrin a6ß4 or integrin a3 genes that Chercheur principals to epidermal loss and cause the skin to blister easily. There is no established cure for JEB and the treatment is palliative, mainly with bandages to protect epithelial wounds. As a continuity of our current clinical trial on the dystrophic form of epidermolysis bullosa by using an innovative approach to treat this skin condition, we aim to regenerate a fully functional epidermis for JEB patients by gene correcting their epidermal cells in the lab and use them to produce an artificial skin substitute. For this, the normal copy of the responsible gene will be delivered in JEB cells using a safe self inactivated retrovirus. The transduced cells will be used to produce sheets of skin using the autologous self-assembly method invented in the LOEX. The functionality and the mechanical properties of the produced gene corrected skin equivalents will be assessed. Until now, we recruited one JEB patient, established a cell biobank and characterize the skin cells. In a long term, the gene corrected skin substitute will be grafted in mice to determine if it safe to trial in JEB patients by gafting on wounds. If successful, this approach would provide a therapeutic option for skin lesions of JEB patients. |
01/01/1970 |
31/03/2027 |
| 2025 |
Lucie Germain (P) |
Université Laval |
Subvention de soutien aux projets à fort impact |
Germain |
Chercheuse principale |
Jason Guertin, Julie Fradette, Lucie Germain, Ma'n Zawati, Véronique Moulin |
245,840.00 |
Toward a combined gene therapy and tissue engineering novel treatment for junctional epidermolysis bullosa |
Guérison des plaies |
Épidermolyse bulleuse jonctionnelle, ingénierie tissulaire, thérapie génique, cellules souches, vecteur rétroviral, substitut cutané |
Junctional epidermolysis bullosa (JEB) is a rare genetic disease characterized by presence of bullae at birth, lack of scarring of the lesions, and early death. It is caused by genetic changes in the LAMB3, COL17A1, LAMC2, LAMA3, integrin a6ß4 or integrin a3 genes that Chercheur principals to epidermal loss and cause the skin to blister easily. There is no established cure for JEB and the treatment is palliative, mainly with bandages to protect epithelial wounds. As a continuity of our current clinical trial on the dystrophic form of epidermolysis bullosa by using an innovative approach to treat this skin condition, we aim to regenerate a fully functional epidermis for JEB patients by gene correcting their epidermal cells in the lab and use them to produce an artificial skin substitute. For this, the normal copy of the responsible gene will be delivered in JEB cells using a safe self inactivated retrovirus. The transduced cells will be used to produce sheets of skin using the autologous self-assembly method invented in the LOEX. The functionality and the mechanical properties of the produced gene corrected skin equivalents will be assessed. Until now, we recruited one JEB patient, established a cell biobank and characterize the skin cells. In a long term, the gene corrected skin substitute will be grafted in mice to determine if it safe to trial in JEB patients by gafting on wounds. If successful, this approach would provide a therapeutic option for skin lesions of JEB patients. |
01/01/1970 |
31/03/2027 |
| 2025 |
Ma'n Zawati (C) |
Université McGill |
Subvention de soutien aux projets à fort impact |
Germain |
Cochercheuse |
Jason Guertin, Julie Fradette, Lucie Germain, Ma'n Zawati, Véronique Moulin |
6,000.00 |
Toward a combined gene therapy and tissue engineering novel treatment for junctional epidermolysis bullosa |
Guérison des plaies |
Épidermolyse bulleuse jonctionnelle, ingénierie tissulaire, thérapie génique, cellules souches, vecteur rétroviral, substitut cutané |
Junctional epidermolysis bullosa (JEB) is a rare genetic disease characterized by presence of bullae at birth, lack of scarring of the lesions, and early death. It is caused by genetic changes in the LAMB3, COL17A1, LAMC2, LAMA3, integrin a6ß4 or integrin a3 genes that Chercheur principals to epidermal loss and cause the skin to blister easily. There is no established cure for JEB and the treatment is palliative, mainly with bandages to protect epithelial wounds. As a continuity of our current clinical trial on the dystrophic form of epidermolysis bullosa by using an innovative approach to treat this skin condition, we aim to regenerate a fully functional epidermis for JEB patients by gene correcting their epidermal cells in the lab and use them to produce an artificial skin substitute. For this, the normal copy of the responsible gene will be delivered in JEB cells using a safe self inactivated retrovirus. The transduced cells will be used to produce sheets of skin using the autologous self-assembly method invented in the LOEX. The functionality and the mechanical properties of the produced gene corrected skin equivalents will be assessed. Until now, we recruited one JEB patient, established a cell biobank and characterize the skin cells. In a long term, the gene corrected skin substitute will be grafted in mice to determine if it safe to trial in JEB patients by gafting on wounds. If successful, this approach would provide a therapeutic option for skin lesions of JEB patients. |
01/01/1970 |
31/03/2027 |
| 2025 |
Véronique Moulin (C) |
Université Laval |
Subvention de soutien aux projets à fort impact |
Germain |
Cochercheuse |
Jason Guertin, Julie Fradette, Lucie Germain, Ma'n Zawati, Véronique Moulin |
1,000.00 |
Toward a combined gene therapy and tissue engineering novel treatment for junctional epidermolysis bullosa |
Guérison des plaies |
Épidermolyse bulleuse jonctionnelle, ingénierie tissulaire, thérapie génique, cellules souches, vecteur rétroviral, substitut cutané |
Junctional epidermolysis bullosa (JEB) is a rare genetic disease characterized by presence of bullae at birth, lack of scarring of the lesions, and early death. It is caused by genetic changes in the LAMB3, COL17A1, LAMC2, LAMA3, integrin a6ß4 or integrin a3 genes that Chercheur principals to epidermal loss and cause the skin to blister easily. There is no established cure for JEB and the treatment is palliative, mainly with bandages to protect epithelial wounds. As a continuity of our current clinical trial on the dystrophic form of epidermolysis bullosa by using an innovative approach to treat this skin condition, we aim to regenerate a fully functional epidermis for JEB patients by gene correcting their epidermal cells in the lab and use them to produce an artificial skin substitute. For this, the normal copy of the responsible gene will be delivered in JEB cells using a safe self inactivated retrovirus. The transduced cells will be used to produce sheets of skin using the autologous self-assembly method invented in the LOEX. The functionality and the mechanical properties of the produced gene corrected skin equivalents will be assessed. Until now, we recruited one JEB patient, established a cell biobank and characterize the skin cells. In a long term, the gene corrected skin substitute will be grafted in mice to determine if it safe to trial in JEB patients by gafting on wounds. If successful, this approach would provide a therapeutic option for skin lesions of JEB patients. |
01/01/1970 |
31/03/2027 |
| 2025 |
Christos Boutopoulos (C) |
CIUSSS de l'Est-de-l'Île-de-Montréal (Hôpital Maisonneuve-Rosemont) |
Subvention de soutien aux projets à fort impact |
Griffith |
Cochercheuse |
Christos Boutopoulos, Denis-Claude Roy, Marie-Claude Robert, May Griffith |
83,200.00 |
Direct Bioprinting for Regenerating the Cornea with Inflammation-Suppressing Bioink |
Maladies oculaires |
Stylo à bio-encre assisté par laser, bio-imprimante, suppression de l’inflammation, bio-encre, cellules souches, lapin |
Currently, corneal donor transplantation is the only widely accepted treatment for corneal blindness, but there is a severe global shortage. Our team previously discovered that the human cornea can be stimulated to regrow from the inside by implanting cell-free biosynthetic hydrogels made from recombinant human collagen. However, while solid implants were successful, they need a cornea surgeon and operating room for treating patients. We have developed LiQD Cornea, a fully synthetic injectable hydrogel to replace traditional corneal transplantation, by treating cornea blindness on an outpatient basis in any setting to regenerate their pathologic corneas. This will provide accessibility to patients who otherwise would not be treated. Our LiQD Cornea will fill wounds, ulcers, perforations before a patient progresses to needing transplantation, with promising results from a large animal pre-clinical study. However, we show that precision filling is needed for rapid healing to prevent infection. Controlling inflammation while giving a smooth surface can be achieved through our novel Laser-BioPen and the new bioink containing with MSC stem cells or their exosome products. At the end of the project, we aim to have a potential therapy that can help regenerate corneal tissue and nerves even in patients with severely inflamed eyes. If successful, this therapy can be extended to treatment of other conditions and other organs. |
01/01/1970 |
31/03/2027 |
| 2025 |
Denis-Claude Roy (C) |
CIUSSS de l'Est-de-l'Île-de-Montréal (Hôpital Maisonneuve-Rosemont) |
Subvention de soutien aux projets à fort impact |
Griffith |
Cochercheuse |
Christos Boutopoulos, Denis-Claude Roy, Marie-Claude Robert, May Griffith |
45,050.00 |
Direct Bioprinting for Regenerating the Cornea with Inflammation-Suppressing Bioink |
Maladies oculaires |
Stylo à bio-encre assisté par laser, bio-imprimante, suppression de l’inflammation, bio-encre, cellules souches, lapin |
Currently, corneal donor transplantation is the only widely accepted treatment for corneal blindness, but there is a severe global shortage. Our team previously discovered that the human cornea can be stimulated to regrow from the inside by implanting cell-free biosynthetic hydrogels made from recombinant human collagen. However, while solid implants were successful, they need a cornea surgeon and operating room for treating patients. We have developed LiQD Cornea, a fully synthetic injectable hydrogel to replace traditional corneal transplantation, by treating cornea blindness on an outpatient basis in any setting to regenerate their pathologic corneas. This will provide accessibility to patients who otherwise would not be treated. Our LiQD Cornea will fill wounds, ulcers, perforations before a patient progresses to needing transplantation, with promising results from a large animal pre-clinical study. However, we show that precision filling is needed for rapid healing to prevent infection. Controlling inflammation while giving a smooth surface can be achieved through our novel Laser-BioPen and the new bioink containing with MSC stem cells or their exosome products. At the end of the project, we aim to have a potential therapy that can help regenerate corneal tissue and nerves even in patients with severely inflamed eyes. If successful, this therapy can be extended to treatment of other conditions and other organs. |
01/01/1970 |
31/03/2027 |
| 2025 |
Marie-Claude Robert (C) |
Université de Montréal |
Subvention de soutien aux projets à fort impact |
Griffith |
Cochercheuse |
Christos Boutopoulos, Denis-Claude Roy, Marie-Claude Robert, May Griffith |
73,376.00 |
Direct Bioprinting for Regenerating the Cornea with Inflammation-Suppressing Bioink |
Maladies oculaires |
Stylo à bio-encre assisté par laser, bio-imprimante, suppression de l’inflammation, bio-encre, cellules souches, lapin |
Currently, corneal donor transplantation is the only widely accepted treatment for corneal blindness, but there is a severe global shortage. Our team previously discovered that the human cornea can be stimulated to regrow from the inside by implanting cell-free biosynthetic hydrogels made from recombinant human collagen. However, while solid implants were successful, they need a cornea surgeon and operating room for treating patients. We have developed LiQD Cornea, a fully synthetic injectable hydrogel to replace traditional corneal transplantation, by treating cornea blindness on an outpatient basis in any setting to regenerate their pathologic corneas. This will provide accessibility to patients who otherwise would not be treated. Our LiQD Cornea will fill wounds, ulcers, perforations before a patient progresses to needing transplantation, with promising results from a large animal pre-clinical study. However, we show that precision filling is needed for rapid healing to prevent infection. Controlling inflammation while giving a smooth surface can be achieved through our novel Laser-BioPen and the new bioink containing with MSC stem cells or their exosome products. At the end of the project, we aim to have a potential therapy that can help regenerate corneal tissue and nerves even in patients with severely inflamed eyes. If successful, this therapy can be extended to treatment of other conditions and other organs. |
01/01/1970 |
31/03/2027 |
| 2025 |
May Griffith (P) |
CIUSSS de l'Est-de-l'Île-de-Montréal (Hôpital Maisonneuve-Rosemont) |
Subvention de soutien aux projets à fort impact |
Griffith |
Chercheuse principale |
Christos Boutopoulos, Denis-Claude Roy, Marie-Claude Robert, May Griffith |
67,408.00 |
Direct Bioprinting for Regenerating the Cornea with Inflammation-Suppressing Bioink |
Maladies oculaires |
Stylo à bio-encre assisté par laser, bio-imprimante, suppression de l’inflammation, bio-encre, cellules souches, lapin |
Currently, corneal donor transplantation is the only widely accepted treatment for corneal blindness, but there is a severe global shortage. Our team previously discovered that the human cornea can be stimulated to regrow from the inside by implanting cell-free biosynthetic hydrogels made from recombinant human collagen. However, while solid implants were successful, they need a cornea surgeon and operating room for treating patients. We have developed LiQD Cornea, a fully synthetic injectable hydrogel to replace traditional corneal transplantation, by treating cornea blindness on an outpatient basis in any setting to regenerate their pathologic corneas. This will provide accessibility to patients who otherwise would not be treated. Our LiQD Cornea will fill wounds, ulcers, perforations before a patient progresses to needing transplantation, with promising results from a large animal pre-clinical study. However, we show that precision filling is needed for rapid healing to prevent infection. Controlling inflammation while giving a smooth surface can be achieved through our novel Laser-BioPen and the new bioink containing with MSC stem cells or their exosome products. At the end of the project, we aim to have a potential therapy that can help regenerate corneal tissue and nerves even in patients with severely inflamed eyes. If successful, this therapy can be extended to treatment of other conditions and other organs. |
01/01/1970 |
31/03/2027 |
| 2025 |
Elie Haddad (P) |
Centre hospitalier universitaire Sainte-Justine |
Subvention de soutien aux projets à fort impact |
Haddad |
Chercheur principal |
Elie Haddad |
270,000.00 |
Harnessing Synthetic Specific Promoters for Targeted Gene Therapy in Hemophagocytic Lymphohistiocytosis (HLH) |
Trouble du système immunitaire |
Cellules souches modifiées, promoteurs spécifiques synthétiques, thérapie génique, lymphohistiocytose hémophagocytaire, erreur innée de l’immunité, cellules souches hématopoïétiques |
Hemophagocytic Lymphohistiocytosis (HLH) is a rare and severe disease, affecting children having inherited a mutated gene, that causes the immune system to overreact to infections. This overreaction can Chercheur principal to widespread inflammation and even organ failure, making HLH life-threatening if not treated. Currently, the main treatment is a stem cell transplant from a donor, but this procedure comes with serious risks due to the body's hyper-inflammatory response. A promising alternative is gene therapy, where the patient’s own cells are modified to correct the underlying genetic defect. However, the challenge with gene therapy for HLH is that the gene responsible for the disease (called perforin) needs to be expressed only in certain immune cells, the T-cells and NK cells. If perforin is expressed in the wrong cells, it could Chercheur principal to harmful side effects.
We propose to develop a more precise gene therapy approach. We designed a way to express the perforin gene only to the right immune cells by using a special "switch" (called a promoter) that controls the gene's expression. This new strategy could avoid unwanted side effects while restoring immune system function. This new approach will be tested in laboratory mice to see if it can prevent the deadly inflammatory reactions, and in patients’ cells to test if it can correct Perforin expression and function. If successful, this therapy could offer a safer and effective treatment for HLH and potentially other immune-related diseases |
01/01/1970 |
31/03/2027 |
| 2025 |
Bowen Li (C) |
University of Toronto |
Subvention de soutien aux projets à fort impact |
Laflamme |
Cochercheur |
Bowen Li, Michael Laflamme |
152,232.00 |
RNA-based strategies to promote the engraftment of stem cell-derived cardiomyocytes |
Troubles cardiaques |
Cellules souches pluripotentes, cardiomyocytes, greffe de cellules, ARN circulaire, ARN modifié, infarctus du myocarde |
Heart failure is a Chercheur principaling cause of death in Canada, placing a heavy burden on patients, families, and the healthcare system. While stem cell therapy holds great promise for heart regeneration, a major hurdle is that many transplanted cells die shortly after being delivered. To address this, researchers are exploring ways to boost cell survival. _x000D_
_x000D_
One promising strategy involves co-delivering cells with select proteins that protect cells, but protein rapidly diffuses away once it’s delivered to the cells. This project focuses on a cutting-edge solution: pre-treating the cells with circular RNA (circRNA) that encodes for protective proteins. Unlike other forms of RNA, circRNA is more stable and allows for long-lasting production of desired proteins by the cell themselves. Our team of Canadian regenerative medicine researchers aims to leverage circRNA technology to enhance the survival and integration of regenerative cells in injured hearts. _x000D_
_x000D_
The project involves three key steps: _x000D_
1. Creating optimized circRNAs for heart cells _x000D_
2. Developing advanced delivery systems using nanoparticles _x000D_
3. Testing the therapy in a rat model of heart attack. _x000D_
_x000D_
By combining expertise in RNA science and regenerative medicine, our team will advance a bold solution to improve stem cell therapy for heart failure, addressing one of the nation’s most pressing health challenges while showcasing our Chercheur principalership in biomedical innovation. |
01/01/1970 |
31/03/2027 |
| 2025 |
Michael Laflamme (P) |
University Health Network |
Subvention de soutien aux projets à fort impact |
Laflamme |
Chercheur principal |
Bowen Li, Michael Laflamme |
117,448.00 |
RNA-based strategies to promote the engraftment of stem cell-derived cardiomyocytes |
Troubles cardiaques |
Cellules souches pluripotentes, cardiomyocytes, greffe de cellules, ARN circulaire, ARN modifié, infarctus du myocarde |
Heart failure is a Chercheur principaling cause of death in Canada, placing a heavy burden on patients, families, and the healthcare system. While stem cell therapy holds great promise for heart regeneration, a major hurdle is that many transplanted cells die shortly after being delivered. To address this, researchers are exploring ways to boost cell survival. _x000D_
_x000D_
One promising strategy involves co-delivering cells with select proteins that protect cells, but protein rapidly diffuses away once it’s delivered to the cells. This project focuses on a cutting-edge solution: pre-treating the cells with circular RNA (circRNA) that encodes for protective proteins. Unlike other forms of RNA, circRNA is more stable and allows for long-lasting production of desired proteins by the cell themselves. Our team of Canadian regenerative medicine researchers aims to leverage circRNA technology to enhance the survival and integration of regenerative cells in injured hearts. _x000D_
_x000D_
The project involves three key steps: _x000D_
1. Creating optimized circRNAs for heart cells _x000D_
2. Developing advanced delivery systems using nanoparticles _x000D_
3. Testing the therapy in a rat model of heart attack. _x000D_
_x000D_
By combining expertise in RNA science and regenerative medicine, our team will advance a bold solution to improve stem cell therapy for heart failure, addressing one of the nation’s most pressing health challenges while showcasing our Chercheur principalership in biomedical innovation. |
01/01/1970 |
31/03/2027 |
| 2025 |
Kelly McNagny (P) |
University of British Columbia |
Subvention de soutien aux projets à fort impact |
McNagny |
Chercheuse principale |
Kelly McNagny, Peter Zandstra |
135,000.00 |
Harnessing Stem Cell-Derived Tissue-Resident Innate Lymphoid Cells to Target and Eliminate Solid Tumors |
Cancer |
Immunothérapie anticancéreuse, cellules lymphoïdes innées, différenciation de cellules souches, thérapie cellulaire, ingénierie des cellules immunitaires, médecine régénératrice, tumeurs solides |
Innate lymphoid cells (ILCs) are a newly discovered type of immune cell that, act as our body's first line of defence against infections. ILCs also play a crucial role in maintaining normal tissue health and fighting cancer. When it comes to solid tumours, ILCs infiltrate the tumour environment and attack cancer cells by releasing substances that inhibit tumour growth, presenting tumour fragments to other immune cells, and recruiting additional immune reinforcements. Our goal here is to harness the potential of ILCs for cancer treatment, particularly for solid tumours, by equipping them with a specialized tool known as a chimeric antigen receptor (CAR). CARs will further enable ILCs to selectively recognize and bind to tumor cells, and trigger their tumor-killing functions. We have recently discovered that ILCs can be manufactured from induced pluripotent stem cells (iPSCs), which are a versatile, renewable source of cells capable of developing into any cell type. In this study, we plan to optimize culture conditions for their development and genetically modify these cells in a way that maximizes their efficacy in killing tumours. We will then evaluate CAR-ILCs tumour-killing efficiency in both cell cultures and preclinical animal models. This will lay the groundwork for creating a whole new class of immune cells with the potential to target and treat aggressive cancers. |
01/01/1970 |
31/03/2027 |
| 2025 |
Peter Zandstra (C) |
University of British Columbia |
Subvention de soutien aux projets à fort impact |
McNagny |
Cochercheuse |
Kelly McNagny, Peter Zandstra |
135,000.00 |
Harnessing Stem Cell-Derived Tissue-Resident Innate Lymphoid Cells to Target and Eliminate Solid Tumors |
Cancer |
Immunothérapie anticancéreuse, cellules lymphoïdes innées, différenciation de cellules souches, thérapie cellulaire, ingénierie des cellules immunitaires, médecine régénératrice, tumeurs solides |
Innate lymphoid cells (ILCs) are a newly discovered type of immune cell that, act as our body's first line of defence against infections. ILCs also play a crucial role in maintaining normal tissue health and fighting cancer. When it comes to solid tumours, ILCs infiltrate the tumour environment and attack cancer cells by releasing substances that inhibit tumour growth, presenting tumour fragments to other immune cells, and recruiting additional immune reinforcements. Our goal here is to harness the potential of ILCs for cancer treatment, particularly for solid tumours, by equipping them with a specialized tool known as a chimeric antigen receptor (CAR). CARs will further enable ILCs to selectively recognize and bind to tumor cells, and trigger their tumor-killing functions. We have recently discovered that ILCs can be manufactured from induced pluripotent stem cells (iPSCs), which are a versatile, renewable source of cells capable of developing into any cell type. In this study, we plan to optimize culture conditions for their development and genetically modify these cells in a way that maximizes their efficacy in killing tumours. We will then evaluate CAR-ILCs tumour-killing efficiency in both cell cultures and preclinical animal models. This will lay the groundwork for creating a whole new class of immune cells with the potential to target and treat aggressive cancers. |
01/01/1970 |
31/03/2027 |
| 2025 |
Fabio Rossi (P) |
University of British Columbia |
Subvention de soutien aux projets à fort impact |
Rossi |
Chercheur principal |
Fabio Rossi |
270,000.00 |
Engineering hPS derived myogenic progenitors to deliver anti-fibrotic molecules |
Troubles musculo-squelettiques |
CSPh, fibrose, scFv, muscles, greffe |
Fibrosis is an important problem affecting most chronic diseases. In addition it drives scar formation when significant amount of tissue is lost. Both these issues are evident in the context of skeletal muscle, where muscular dystrophies as well as the loss of large volume of tissue due to trauma or infection Chercheur principal to a fibrotic response that interferes with therapies. Key drivers of fibrosis are the family of factors called TGFbeta. Blockade of these factors can reduce fibrosis but Chercheur principals to a number of side effects due to their involvement in controlling immunity. Together with a commercial partner we have generated a molecule that targets some members of this family, but leaves untouched those involved in immunity. Here we propose to deliver cells engineered to produce this molecule to skeletal muscle, to test if they reduce fibrosis. This will be done by assembling muscle tissue in the lab starting from stem cells, and transplanting it into large muscle defects that would normally heal through scarring. If successful, this approach may offer solutions well beyond skeletal muscle, as other types of cell could be engineered to reduce fibrosis using this approach. |
01/01/1970 |
31/03/2027 |
| 2025 |
Cheryle Seguin (P) |
University of Western Ontario |
Subvention de soutien aux projets à fort impact |
Seguin |
Chercheuse principale |
Cheryle Seguin |
270,000.00 |
Delivery of induced pluripotent stem cells in cell-instructive composite hydrogels for nucleus pulposus regeneration |
Troubles musculo-squelettiques |
Disques intervertébraux, cellules souches pluripotentes induites, hydrogels mécaniquement résistants, tissus décellularisés, grands modèles animaux |
Chronic back pain associated with intervertebral disc (IVD) degeneration is a debilitating condition that negatively impacts the quality of life of many Canadians. Current treatment strategies focusing on pain management or surgical intervention have limited efficacy and can Chercheur principal to numerous complications. Cell-based therapies involving the delivery of proregenerative stem cells into the inner nucleus pulposus (NP) region of the IVD hold promise as a new approach to modify the progression of the disease and promote tissue repair, with the goal of improving function and reducing pain. This research project brings together an interdisciplinary team to develop novel cell-instructive biomaterials platforms for the delivery of induced pluripotent stem cell (iPSC)-derived cells to the NP region to promote IVD regeneration. These biomaterial platforms are designed to mimic the properties of healthy human NP, be injectable to enable minimally-invasive delivery, and rapidly form a gel at body temperature to encapsulate the regenerative cells and support their viability and function. Our research will specifically compare progenitor notochord cells to more mature NP cells derived from iPSC, to determine the optimal target cell type for delivery. We will perform in-depth testing in vitro using specialized bioreactor systems to culture cell containing composite gels under conditions modelling the native IVD environment, as well as conduct proof-of-concept testing in a large animal model. |
01/01/1970 |
31/03/2027 |
| 2025 |
Michael Kallos (C) |
University of Calgary |
Subvention de soutien aux projets à fort impact |
Shakiba |
Cochercheuse |
Michael Kallos, Nika Shakiba, Sidhartha Goyal |
97,000.00 |
Bioreactor bottlenecks: selection for aberrant cells in pluripotent stem cell expansion |
Multiples maladies |
Cellules souches pluripotentes, bioréacteur, expansion, bioingénierie des cellules souches, biologie des systèmes, biologie de synthèse, attribution d’une signature ADN |
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to understand the impact of culture parameters on variant growth. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at their growth in bioreactors. Concurrently, we will develop a computational framework to predict the risk that variants will contaminate hPSC batches. Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world Chercheur principaler in cell therapy manufacturing for regenerative medicine. |
01/01/1970 |
31/03/2027 |
| 2025 |
Nika Shakiba (P) |
University of British Columbia |
Subvention de soutien aux projets à fort impact |
Shakiba |
Chercheuse principale |
Michael Kallos, Nika Shakiba, Sidhartha Goyal |
171,000.00 |
Bioreactor bottlenecks: selection for aberrant cells in pluripotent stem cell expansion |
Multiples maladies |
Cellules souches pluripotentes, bioréacteur, expansion, bioingénierie des cellules souches, biologie des systèmes, biologie de synthèse, attribution d’une signature ADN |
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to understand the impact of culture parameters on variant growth. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at their growth in bioreactors. Concurrently, we will develop a computational framework to predict the risk that variants will contaminate hPSC batches. Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world Chercheur principaler in cell therapy manufacturing for regenerative medicine. |
01/01/1970 |
31/03/2027 |
| 2025 |
Sidhartha Goyal (C) |
University of Toronto |
Subvention de soutien aux projets à fort impact |
Shakiba |
Cochercheuse |
Michael Kallos, Nika Shakiba, Sidhartha Goyal |
2,000.00 |
Bioreactor bottlenecks: selection for aberrant cells in pluripotent stem cell expansion |
Multiples maladies |
Cellules souches pluripotentes, bioréacteur, expansion, bioingénierie des cellules souches, biologie des systèmes, biologie de synthèse, attribution d’une signature ADN |
Human pluripotent stem cells (hPSCs) have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function. With several clinical trials underway, such as the transplantation of beta cells derived from hPSCs to treat diabetes, clinical demand for hPSCs is growing._x000D_
_x000D_
Canada’s booming biotechnology sector is strategically positioned to meet this demand, with the capability to grow billions of hPSCs for cell therapy production. However, these pipelines are plagued by “variants”, which emerge as hPSCs divide and acquire undesirable genetic changes. Cancer-like variants outgrow normal hPSCs and go on to overtake the cell batch, rendering it unsuitable for clinical use. To tackle this significant challenge, we will use a bioengineering approach to understand the impact of culture parameters on variant growth. We will use our existing cutting-edge genetic tools to track hPSCs, providing a high-resolution look at their growth in bioreactors. Concurrently, we will develop a computational framework to predict the risk that variants will contaminate hPSC batches. Our results will enable the safe and reliable large-scale production of hPSCs, bolstering Canada’s position as a world Chercheur principaler in cell therapy manufacturing for regenerative medicine. |
01/01/1970 |
31/03/2027 |
| 2025 |
Peter Zandstra (P) |
University of British Columbia |
Subvention de soutien aux projets à fort impact |
Zandstra |
Chercheur principal |
Peter Zandstra |
270,000.00 |
Automating Systems Biology and Machine Learning for Multiscale Regulatory Network Discovery in Stem Cell Differentiation |
Multiples maladies |
Développement de cellules souches; différenciation; cadres réglementaires; thérapie cellulaire; apprentissage machine; IA; biofabrication automatisée |
Stem cells hold immense promise for developing therapies to treat a wide range of diseases. However, the process of designing protocols to guide stem cells into becoming specific cell types is slow, costly, and heavily reliant on trial-and-error methods. Current approaches often require specialized knowledge and significant experimental resources, limiting innovation in regenerative medicine.
To address this challenge, we propose IQCELL 2.0, a cutting-edge platform that combines artificial intelligence and systems biology to accelerate the discovery of gene regulatory networks (GRNs)—the complex systems that control how cells make decisions about their fate. Our platform integrates Systems Biology-Informed Neural Networks (SBINNs) with experimental data to predict and optimize differentiation protocols with unprecedented accuracy and scalability. By automating this process, IQCELL 2.0 reduces the need for labor-intensive wet-lab experimentation, enabling faster and more cost-effective development of stem cell-based therapies.
In this project, we will refine and validate IQCELL 2.0 using human T-cell data and expand its capabilities to model differentiation for other cell types, such as B-cells and liver cells. Collaborations with Chercheur principaling research and commercial partners will ensure the platform’s applicability to real-world challenges, including immunotherapy and regenerative medicine.
Ultimately, IQCELL 2.0 aims to transform stem cell research by making advanced differentiation modeling accessible, predictive, and actionable—enabling researchers to automate the design, optimization, and scalable production of functional cell types for therapeutic and translational applications. |
01/01/1970 |
31/03/2027 |
| 2025 |
Marya Ahmed (P) |
University of Alberta |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Ahmed |
Chercheuse principale |
Marya Ahmed |
162,000.00 |
Stem Cell Cryopreservation Efficacies of Polymeric Nanogels |
Diabète |
Cryoconservation des CSPi, nanogels polymériques, îlots-CS, translation clinique, diabète de type 1 |
The cell based therapeutics can revolutionize the field of traditional medicine with the opportunities to treat incurable diseases and to improve patient compliance and comfort. For example, at present regular injections of insulin is only feasible option to treat type 1 diabetes. The implantation of pancreas-derived cells in patients can enable insulin formation in the body, eliminating the need to inject insulin, improving the life quality of patients. However, harvesting and proper storage of pancreas derived cells until the need arise is difficult. At present, the only storage method for all cell based products is their freezing at low temperatures in the presence of reagents that help with the freezing process, however these reagents tend to kill the cells during freezing and thawing and can cause allergic reactions in patients. This project will develop non-toxic naturally-derived gels for freezing a variety of cell based therapeutics (specifically pancreatic clusters) and gel formulations with best cell storage capability will be identified. The identified gel based products will be evaluated for commercial scale production. The training of students on state-of-art techniques will produce highly qualified personnel who will contribute to the Canadian economy. The success of this project will provide new intellectual property that will be of interest to researchers and companies in regenerative medicine in Canada and across the globe. |
01/01/1970 |
31/03/2027 |
| 2025 |
Andras Nagy (C) |
Sinai Health System |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Hoesli |
Cochercheuse |
Andras Nagy, André Bégin-Drolet, Corinne Hoesli, Richard Leask, Steven Paraskevas |
6,700.00 |
Vascular lattice bioartificial pancreas for diabetes cellular therapy |
Diabète |
Îlots issus de cellules souches, encapsulation, greffon vasculaire, préclinique - rat, préclinique - porc, hydrogel, impression 3D |
Type 1 diabetes is an autoimmune disease that Chercheur principals to loss of the insulin-producing cells in the pancreas. These cells are found in cell clusters called islets of Langerhans. Most people with type 1 diabetes rely on daily insulin administration to survive. Even with careful management, blood glucose fluctuations that remain with insulin therapy can be life-threatening or cause chronic complications. Islet transplantation can significantly improve blood glucose control and even allow some recipients to live without insulin injections. Since the islets used in these transplants are obtained from recently deceased organ donors, few can benefit from this therapy._x000D_
_x000D_
Lab-grown stem cells offer a potentially unlimited source of islets for transplantation. Since these are a higher-risk source than islets from donors, containment within a device could allow retrieval if there are complications. These encapsulation devices typically limit blood supply. We propose a device where the stem cell-derived islets are placed around a vascular graft. The pre-established vasculature can improve graft survival and speed of insulin responses. In this project, we will optimize our device design and conduct studies in large animals._x000D_
_x000D_
This project could Chercheur principal to better survival and function of stem cell-derived islets. The device could provide long-term blood glucose control without external intervention. The project can also pave the way for other engineered human-scale bioartificial organs._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
André Bégin-Drolet (C) |
Université Laval |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Hoesli |
Cochercheuse |
Andras Nagy, André Bégin-Drolet, Corinne Hoesli, Richard Leask, Steven Paraskevas |
4,850.00 |
Vascular lattice bioartificial pancreas for diabetes cellular therapy |
Diabète |
Îlots issus de cellules souches, encapsulation, greffon vasculaire, préclinique - rat, préclinique - porc, hydrogel, impression 3D |
Type 1 diabetes is an autoimmune disease that Chercheur principals to loss of the insulin-producing cells in the pancreas. These cells are found in cell clusters called islets of Langerhans. Most people with type 1 diabetes rely on daily insulin administration to survive. Even with careful management, blood glucose fluctuations that remain with insulin therapy can be life-threatening or cause chronic complications. Islet transplantation can significantly improve blood glucose control and even allow some recipients to live without insulin injections. Since the islets used in these transplants are obtained from recently deceased organ donors, few can benefit from this therapy._x000D_
_x000D_
Lab-grown stem cells offer a potentially unlimited source of islets for transplantation. Since these are a higher-risk source than islets from donors, containment within a device could allow retrieval if there are complications. These encapsulation devices typically limit blood supply. We propose a device where the stem cell-derived islets are placed around a vascular graft. The pre-established vasculature can improve graft survival and speed of insulin responses. In this project, we will optimize our device design and conduct studies in large animals._x000D_
_x000D_
This project could Chercheur principal to better survival and function of stem cell-derived islets. The device could provide long-term blood glucose control without external intervention. The project can also pave the way for other engineered human-scale bioartificial organs._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Corinne Hoesli (P) |
Université McGill |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Hoesli |
Chercheuse principale |
Andras Nagy, André Bégin-Drolet, Corinne Hoesli, Richard Leask, Steven Paraskevas |
125,450.00 |
Vascular lattice bioartificial pancreas for diabetes cellular therapy |
Diabète |
Îlots issus de cellules souches, encapsulation, greffon vasculaire, préclinique - rat, préclinique - porc, hydrogel, impression 3D |
Type 1 diabetes is an autoimmune disease that Chercheur principals to loss of the insulin-producing cells in the pancreas. These cells are found in cell clusters called islets of Langerhans. Most people with type 1 diabetes rely on daily insulin administration to survive. Even with careful management, blood glucose fluctuations that remain with insulin therapy can be life-threatening or cause chronic complications. Islet transplantation can significantly improve blood glucose control and even allow some recipients to live without insulin injections. Since the islets used in these transplants are obtained from recently deceased organ donors, few can benefit from this therapy._x000D_
_x000D_
Lab-grown stem cells offer a potentially unlimited source of islets for transplantation. Since these are a higher-risk source than islets from donors, containment within a device could allow retrieval if there are complications. These encapsulation devices typically limit blood supply. We propose a device where the stem cell-derived islets are placed around a vascular graft. The pre-established vasculature can improve graft survival and speed of insulin responses. In this project, we will optimize our device design and conduct studies in large animals._x000D_
_x000D_
This project could Chercheur principal to better survival and function of stem cell-derived islets. The device could provide long-term blood glucose control without external intervention. The project can also pave the way for other engineered human-scale bioartificial organs._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Richard Leask (C) |
Université McGill |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Hoesli |
Cochercheuse |
Andras Nagy, André Bégin-Drolet, Corinne Hoesli, Richard Leask, Steven Paraskevas |
7,500.00 |
Vascular lattice bioartificial pancreas for diabetes cellular therapy |
Diabète |
Îlots issus de cellules souches, encapsulation, greffon vasculaire, préclinique - rat, préclinique - porc, hydrogel, impression 3D |
Type 1 diabetes is an autoimmune disease that Chercheur principals to loss of the insulin-producing cells in the pancreas. These cells are found in cell clusters called islets of Langerhans. Most people with type 1 diabetes rely on daily insulin administration to survive. Even with careful management, blood glucose fluctuations that remain with insulin therapy can be life-threatening or cause chronic complications. Islet transplantation can significantly improve blood glucose control and even allow some recipients to live without insulin injections. Since the islets used in these transplants are obtained from recently deceased organ donors, few can benefit from this therapy._x000D_
_x000D_
Lab-grown stem cells offer a potentially unlimited source of islets for transplantation. Since these are a higher-risk source than islets from donors, containment within a device could allow retrieval if there are complications. These encapsulation devices typically limit blood supply. We propose a device where the stem cell-derived islets are placed around a vascular graft. The pre-established vasculature can improve graft survival and speed of insulin responses. In this project, we will optimize our device design and conduct studies in large animals._x000D_
_x000D_
This project could Chercheur principal to better survival and function of stem cell-derived islets. The device could provide long-term blood glucose control without external intervention. The project can also pave the way for other engineered human-scale bioartificial organs._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Steven Paraskevas (C) |
Institut de recherche du Centre universitaire de santé McGill |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Hoesli |
Cochercheuse |
Andras Nagy, André Bégin-Drolet, Corinne Hoesli, Richard Leask, Steven Paraskevas |
17,500.00 |
Vascular lattice bioartificial pancreas for diabetes cellular therapy |
Diabète |
Îlots issus de cellules souches, encapsulation, greffon vasculaire, préclinique - rat, préclinique - porc, hydrogel, impression 3D |
Type 1 diabetes is an autoimmune disease that Chercheur principals to loss of the insulin-producing cells in the pancreas. These cells are found in cell clusters called islets of Langerhans. Most people with type 1 diabetes rely on daily insulin administration to survive. Even with careful management, blood glucose fluctuations that remain with insulin therapy can be life-threatening or cause chronic complications. Islet transplantation can significantly improve blood glucose control and even allow some recipients to live without insulin injections. Since the islets used in these transplants are obtained from recently deceased organ donors, few can benefit from this therapy._x000D_
_x000D_
Lab-grown stem cells offer a potentially unlimited source of islets for transplantation. Since these are a higher-risk source than islets from donors, containment within a device could allow retrieval if there are complications. These encapsulation devices typically limit blood supply. We propose a device where the stem cell-derived islets are placed around a vascular graft. The pre-established vasculature can improve graft survival and speed of insulin responses. In this project, we will optimize our device design and conduct studies in large animals._x000D_
_x000D_
This project could Chercheur principal to better survival and function of stem cell-derived islets. The device could provide long-term blood glucose control without external intervention. The project can also pave the way for other engineered human-scale bioartificial organs._x000D_ |
01/01/1970 |
31/03/2027 |
| 2025 |
Bruce Verchere (C) |
University of British Columbia |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Levings |
Cochercheuse |
Bruce Verchere, Francis Lynn, Megan Levings, Peter Zandstra |
30,000.00 |
Leveraging stem cells to create an engineered model of type 1 diabetes |
Diabète |
Diabète, auto-immunité, lymphocytes T, cellules présentatrices d’antigènes |
Type 1 diabetes (T1D) is an autoimmune disease in which the body mistakenly attacks the insulin-producing cells in the pancreas. There are many new treatments on the horizon for T1D, such as replacement of insulin-producing cells, and therapies that seek to block autoimmunity, such as so-called “inverse vaccines” and immune cell therapies. However, a major barrier to all these therapies is the lack of an easy-to-use model in which their effects on human cells can be tested. _x000D_
_x000D_
To overcome this barrier, we are establishing a new a model that recreates T1D in the lab. We use stem cells, which are immature cells that can be stimulated to become various cell types, to create the three types of cells that are involved in the disease: insulin-producing cells, and two different types of immune cells, known as T cells and antigen presenting cells. We can then combine these cells in different ways to create a method that resembles what usually happens during autoimmunity. _x000D_
_x000D_
A model of human T1D that can be generated in the lab, will help us test potential treatments and ask questions about why T1D develops, and thus how to prevent it. Thus this research has the potential to support the further development of innovative therapies that may offer new approaches to prevent or treat people with T1D. |
01/01/1970 |
31/03/2027 |
| 2025 |
Francis Lynn (C) |
University of British Columbia |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Levings |
Cochercheuse |
Bruce Verchere, Francis Lynn, Megan Levings, Peter Zandstra |
30,000.00 |
Leveraging stem cells to create an engineered model of type 1 diabetes |
Diabète |
Diabète, auto-immunité, lymphocytes T, cellules présentatrices d’antigènes |
Type 1 diabetes (T1D) is an autoimmune disease in which the body mistakenly attacks the insulin-producing cells in the pancreas. There are many new treatments on the horizon for T1D, such as replacement of insulin-producing cells, and therapies that seek to block autoimmunity, such as so-called “inverse vaccines” and immune cell therapies. However, a major barrier to all these therapies is the lack of an easy-to-use model in which their effects on human cells can be tested. _x000D_
_x000D_
To overcome this barrier, we are establishing a new a model that recreates T1D in the lab. We use stem cells, which are immature cells that can be stimulated to become various cell types, to create the three types of cells that are involved in the disease: insulin-producing cells, and two different types of immune cells, known as T cells and antigen presenting cells. We can then combine these cells in different ways to create a method that resembles what usually happens during autoimmunity. _x000D_
_x000D_
A model of human T1D that can be generated in the lab, will help us test potential treatments and ask questions about why T1D develops, and thus how to prevent it. Thus this research has the potential to support the further development of innovative therapies that may offer new approaches to prevent or treat people with T1D. |
01/01/1970 |
31/03/2027 |
| 2025 |
Megan Levings (P) |
University of British Columbia |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Levings |
Chercheuse principale |
Bruce Verchere, Francis Lynn, Megan Levings, Peter Zandstra |
72,000.00 |
Leveraging stem cells to create an engineered model of type 1 diabetes |
Diabète |
Diabète, auto-immunité, lymphocytes T, cellules présentatrices d’antigènes |
Type 1 diabetes (T1D) is an autoimmune disease in which the body mistakenly attacks the insulin-producing cells in the pancreas. There are many new treatments on the horizon for T1D, such as replacement of insulin-producing cells, and therapies that seek to block autoimmunity, such as so-called “inverse vaccines” and immune cell therapies. However, a major barrier to all these therapies is the lack of an easy-to-use model in which their effects on human cells can be tested. _x000D_
_x000D_
To overcome this barrier, we are establishing a new a model that recreates T1D in the lab. We use stem cells, which are immature cells that can be stimulated to become various cell types, to create the three types of cells that are involved in the disease: insulin-producing cells, and two different types of immune cells, known as T cells and antigen presenting cells. We can then combine these cells in different ways to create a method that resembles what usually happens during autoimmunity. _x000D_
_x000D_
A model of human T1D that can be generated in the lab, will help us test potential treatments and ask questions about why T1D develops, and thus how to prevent it. Thus this research has the potential to support the further development of innovative therapies that may offer new approaches to prevent or treat people with T1D. |
01/01/1970 |
31/03/2027 |
| 2025 |
Peter Zandstra (C) |
University of British Columbia |
Subvention de soutien aux projets à fort impact (cofinancée par Percée DT1) |
Levings |
Cochercheuse |
Bruce Verchere, Francis Lynn, Megan Levings, Peter Zandstra |
30,000.00 |
Leveraging stem cells to create an engineered model of type 1 diabetes |
Diabète |
Diabète, auto-immunité, lymphocytes T, cellules présentatrices d’antigènes |
Type 1 diabetes (T1D) is an autoimmune disease in which the body mistakenly attacks the insulin-producing cells in the pancreas. There are many new treatments on the horizon for T1D, such as replacement of insulin-producing cells, and therapies that seek to block autoimmunity, such as so-called “inverse vaccines” and immune cell therapies. However, a major barrier to all these therapies is the lack of an easy-to-use model in which their effects on human cells can be tested. _x000D_
_x000D_
To overcome this barrier, we are establishing a new a model that recreates T1D in the lab. We use stem cells, which are immature cells that can be stimulated to become various cell types, to create the three types of cells that are involved in the disease: insulin-producing cells, and two different types of immune cells, known as T cells and antigen presenting cells. We can then combine these cells in different ways to create a method that resembles what usually happens during autoimmunity. _x000D_
_x000D_
A model of human T1D that can be generated in the lab, will help us test potential treatments and ask questions about why T1D develops, and thus how to prevent it. Thus this research has the potential to support the further development of innovative therapies that may offer new approaches to prevent or treat people with T1D. |
01/01/1970 |
31/03/2027 |
| 2025 |
Timothy Caulfield (P) |
University of Alberta |
Subvention de soutien aux projets à fort impact: filière des QEJS |
Caulfield |
Chercheur principal |
Timothy Caulfield |
214,930.00 |
Regenerative Medicine, Wellness Influencers, and Scienceploitation |
QEJS |
Médecine régénératrice, industrie du bien-être, fausses informations, communication de la science |
The commercialization and distortion of regenerative medicine (RM) is expanding. While extensive research has analyzed unproven therapies in stem cell clinics, emerging RM contexts include supplementation, longevity discourse, and wellness ideas. Online RM discourse now includes anti-aging and health optimization ideas created by wellness influencers with large audiences and lucrative businesses. This influencer discourse generates public misperceptions of RM, along with promoting products/services that can Chercheur principal to consumer exploitation and physical harm. It fuels distrust of legitimate science and generates revenue for social media platforms. This project aims to map online RM misinformation, critically examining key sources of influence, and the enabling roles of powerful digital platforms. We will explore how RM science is manipulated for profit and analyze the social forces driving misinformation, wellness ideas, and commerce. Our findings will generate engaging knowledge-translation deliverables and guide recommendations for science communication, policy, and regulatory responses to reduce harm. The project will produce a misinformation research website, academic publications and presentations, science communication materials, including a podcast, and policy suggestions. A team of highly skilled experts and partners, including #ScienceUpFirst and BC Cancer, will collaborate to conduct this important research, and enhance the impact and reach of its findings. |
01/01/1970 |
31/03/2027 |
