Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Type 1 diabetes (T1D) is a disease where the insulin-producing cells of the pancreatic islets are destroyed by the immune system, leading to high blood sugar levels. Transplanting islets from donors is an alternative therapy to insulin injections; however, the patient must have their immune system suppressed to prevent graft rejection. The drugs used to suppress the immune system increase the risk for many health complications and are toxic to the transplanted insulin-producing cells. New strategies are being investigated to minimize the use of these drugs, making the procedure safer and prolonging graft survival. Regulatory T cells (Tregs), which are immune-suppressing white blood cells, could potentially be recruited to the graft site to prevent its destruction. The migration of Tregs is directed by proteins called chemokines. CCL22 is a chemokine highly effective in recruiting Tregs. Stem cells can be used to generate stem cell-derived islets and can be genetically modified to have high expression of CCL22. Our goal is to modify CCL22 to reduce its degradation and express this modified version of CCL22 in stem cell-derived islets that we will transplant into mice with T1D. We hypothesize that these transplants will allow mice to regain normal blood sugar levels while recruiting Tregs to the graft, allowing the transplanted cells to survive long-term without administering immunosuppressing drugs. This would make islet replacement therapy a safer and more widely available therapy option for individuals living with T1D.