Congratulations to BC Children’s Hospital researchers who were awarded grants from the Stem Cell Network’s (SCN's) annual funding competition. Our researchers are either principal investigators or co-investigators for five projects that received grants.
The research projects focus on stem cell therapies and/or explore ways of making them more effective or feasible. Four of these projects are focused on diabetes.
One of the grants will fund a first-of-its-kind clinical trial that will recruit Type 1 diabetes patients in British Columbia.
The Stem Cell Network (SCN)’s funds originate from the federal government’s $12 million, two-year investment in stem cell research, announced in March. The grants were announced Nov. 24 in Ottawa by the Honourable Kirsty Duncan, federal Minister of Science.
“These projects encourage partnerships between universities, hospitals and businesses—and that collaboration is a key component of a healthy innovation system,” Minister Duncan said. “Through the Stem Cell Network, people are gaining a better understanding of this promising research, which in turn, helps to inform more effective public policy.”
Michael Rudnicki, Scientific Director of SCN, said research into stem cells is now at a “tipping point, with the potential to see breakthroughs in our generation.”
The projects being led by or involving investigators at the BC Children’s Hospital Research Institute are:
Genetic manipulation of hESC-derived insulin-producing cells to improve graft outcomes
Principal investigator: Bruce Verchere, Investigator, BC Children’s Hospital; Professor, Department of Surgery, UBC
Co-investigators: Megan Levings (Investigator, BC Children’s Hospital; Professor, Department of Surgery, UBC), Francis Lynn (Investigator, BC Children’s Hospital; Associate Professor, Department of Surgery. UBC), Tim Kieffer (Department of Cellular and Physiological Sciences, UBC)
Dr. Verchere’s project will edit the genome of human embryonic stem cells to make insulin-producing cells with better function and survival after transplantation into people with diabetes. They will replace a gene that creates toxic products with a safer gene, and they will insert a gene to protect the transplanted cells from immune attack. With further study, the researchers intend to prepare these modified cells for clinical trial.
Garbage to Gold: Expansion of therapeutic regulatory T cells from discarded thymus
Principal investigator: Megan Levings, Investigator, BC Children’s Hospital; Professor, Department of Surgery, UBC
For many patients with blood cancers, the only option for cure is hematopoietic stem cell transplantation (HSCT), but that can cause the donor immune cells to attack the patient’s healthy tissues – known as “graft-versus-host disease.” HSCT would be safer if we could prevent or reduce graft-versus-host disease without affecting the donor cells’ anti-cancer action. Dr. Levings’s team is developing a novel cellular therapy with regulatory T-cells to treat graft-versus-host disease that results from HSCT, but it is difficult and time-consuming to obtain enough regulatory T-cells with the correct properties. Dr. Levings team has shown that appropriate T-cells can be harvested from the thymus gland, which is discarded in children undergoing heart surgery. In this project, her team will develop methods for large-scale expansion of thymic regulatory T-cells, working with a private sector partner 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 regulatory T-cells can reduce graft-versus-host disease.
A stem cell therapy for insulin replacement in patients with diabetes
Principal Investigator: Tim Kieffer, Professor in the Department of Cellular and Physiological Sciences and member, Life Sciences Institute
Co-principal investigators: David Thompson (Clinical Assistant Professor, Department of Medicine), Graydon Meneilly (Professor and Head, Department of Medicine), Garth Warnock (Professor, Department of Surgery) and Megan Levings (Investigator, BC Children’s Hospital; Professor, Department of Surgery, UBC).
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. This project – along with four others also funded by the SCN this year (see below) – seeks to develop a cell-based therapy for diabetes by transplanting differentiated stem cells under the skin, whereby the cells take over the automatic production of insulin and control of blood sugar levels.
This project will 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. 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.
Optimizing stem cell derived beta-cell therapy for diabetes
Principal Investigator: Tim Kieffer, Professor, Department of Cellular and Physiological Sciences; member, Life Sciences Institute
Co-Principal Investigators: Brad Hoffman (Investigator, BC Children’s Hospital; Associate Professor, Department of Surgery, UBC), James Johnson (Professor, Department of Cellular and Physiological Sciences), Francis Lynn (Investigator, BC Children’s Hospital; Associate Professor, Department of Surgery, UBC)
This project will seek to develop and test what many believe are presently the world’s best protocols for coaxing stem cells towards insulin-producing cells. 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 insulin-producing cells. This team, with its highly complementary skills, is poised to develop methods to manufacture mature insulin-producing cells for what promises to be a new paradigm in diabetes treatment.
Using human pluripotent stem-cell derived cardiomycytes to investigate the mechanisms of ibrutinib-induced atrial fibrillation
Principal investigator: Liam Brunham, Assistant Professor, Department of Medicine; Principal Investigator, Centre for Heart+Lung Innovation
Co-investigators: Zach Laksman (Department of Medicine), Glen Tibbits (Investigator, BC Children’s Hospital; Professor, Biomedical Physiology and Kinesiology, SFU)
Ibrutinib is a new, highly effective medication used to treat blood cancers. However, up to 10 per cent of patients receiving this medication develop atrial fibrillation (AF) that can cause stroke, for unknown reasons. Human pluripotent stem cells (hPSCs) can be used to generate human heart cells (cardiomyocytes) representing different heart chambers, and thus 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. Dr. Brunham’s team aims to use these stem cell-derived cardiomyocytes to explore the mechanisms of this side-effect, allowing predictions about which patients may be most sensitive to ibrutinib, and to identify medications to treat or prevent AF in patients who receive ibrutinib — ultimately making treatment with this important new drug safer and more effective.