Project 446711

Diabetes is caused by the lack of insulin, a hormone produced by the islet ß-cells in the pancreas that regulates blood sugar. In Type 1 Diabetes (T1D, ~10%), the ß-cells are destroyed by one's own immune system. In Type 2 Diabetes (T2D, ~90%), the body becomes more resistant to insulin, increasing the demand and eventually leading to ß-cell damage. Chronically high blood sugar can cause complications such as blindness, amputations, stroke, heart disease, kidney failure and shortened lifespan. Insulin injection is life-saving but remains not a cure. Islet transplant has been successful in treating 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 20 years of experience in islet transplant, our team will take advantage of our expertise in stem cell and islet biology, immunology, and transplantation to address these challenges by developing a stem-cell based therapy to replace or supplement damaged ß-cells in people with all types of diabetes, including T1D, T2D, and surgical diabetes after total pancreatectomy. We propose to manufacture new ß-like cells from their own blood cells, so that they will be accepted by the immune system and no/minimal anti-rejection drugs are needed. In this project, we will conduct a First-in-human trial to implant these cells under the patient's skin and evaluate their safety and preliminary efficacy. Manufacturing protocols will be optimized to allow development and scale-up of clinical grade products for therapy. Being able to transplant an unlimited supply of self-derived islet cells without immunosuppressants is a novel approach to treat all forms of diabetes and could be the world's first functional cure.