Grant: Team Grant: DM/TS - CIHR-JDRF - ß-cell and Pancreatic Islet Physiology

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 such as 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 anti-rejection (immunosuppression) drugs and is limited by the scarcity of organ donors. Building on our 21 years of experience in islet transplant, our team will address these challenges by developing a stem-cell based therapy to replace or supplement damaged Beta-cells in people with various forms of diabetes, including T1D, T2D, and surgical diabetes after total pancreatectomy. We propose to manufacture 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, we will generate 'self'-islets from people with diabetes and implant these cells under the patient's skin. In parallel, we will transplant these cells into rats. We will also test whether these cells function similarly to human islets. We anticipate that this project will establish safety of the manufactured 'self'-islets and that they can produce insulin. This will pave the way to our next step - Health Canada approval for a clinical trial with therapeutic doses to be infused in the liver to assess efficacy of this cell therapy. Being able to transplant an unlimited supply of self-derived islet cells without immunosuppressants is a novel approach to treat various forms of diabetes and could be the world's first functional cure.