Grant: CIHR Fellowship

Islet transplantation offers a potential cure for type 1 diabetes, but there is insufficient donor tissue available for treating the growing number of diabetic patients. Therefore, an alternative source of insulin-producing cells is required to bridge the gap between cell supply and demand. Human embryonic stem cells are an ideal starting material as they have the ability to become any cell type in the body. A protocol for mimicking the natural development of human embryonic stem cells into insulin-producing beta cells in culture has previously been established by other investigators, but these cells form tumours following transplantation in mice. Our research project is designed to improve upon the cultured maturation of human embryonic stem cells towards a pancreatic beta cell type that can be transplanted without the risk of tumour formation. Towards this goal, we have developed a protocol for the step-wise differentiation of human embryonic stem cells into cells that resemble the direct neighbour of beta cells, the alpha cells. The next step is to refine our current differentiation protocol to preferentially produce beta cells that are capable of reversing diabetes. We will focus on proteins called 'transcription factors', which regulate cell fate by orchestrating the expression of specific genes. The levels of individual transcription factors will be manipulated in our differentiating stem cells using viruses, to identify factors that enhance the formation of fully mature, glucose-responsive beta cells. Finally, we will assess the ability of these differentiated cells to safely reverse diabetes following transplantation under the kidney capsule of immunocompromised mice.