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

Diabetes is a debilitating disorder of high blood sugar that afflicts millions of Canadians. People living with type 1 diabetes lack the cells that release the hormone insulin, so multiple daily insulin injections remain the conventional way to control blood sugar levels and survive. Scientists in Edmonton made breakthroughs for the transplant of clusters of insulin-producing cells, called islets. The "Edmonton Protocol" is quick and works remarkably well, such that many islet recipients are able to reduce or even eliminate insulin injections. Unfortunately, the only source of islets for transplant is recently deceased donors and only a tiny fraction of those in need can receive them. There have been remarkable breakthroughs in unraveling the process by which islet cells develop naturally in the body. As a result, it is now possible to replicate this process in the lab with cultured stem cells, culminating in insulin producing cells. Exciting clinical trials are now underway in which islet precursor cells generated from stem cells are loaded into thin devices and implanted under the skin. While initial assessments in patients are encouraging, insulin production from the transplanted cells is currently inadequate to reverse diabetes. Our goal is to utilize our broad expertise and a new lab-based model of human islet development to significantly improve upon the manufacturing of the islets to obtain more robust insulin delivery. To achieve this, we have assembled a team of leading experts who will apply their diverse and complementary skills to develop novel strategies to improve the generation of fully functional stem cell derived islets. In particular, we will engineer new cell culture methods to selectively control islet architecture and enhance cell fitness. Collectively our work may form the basis for new clinical trials in patients with type 1 diabetes, and ultimately generate an effective therapy that will free Canadians from insulin injections.