Grant: Proof of Principle Program - Phase I

In type 1 diabetes mellitus the insulin-producing islets cells of the pancreas have been mistakenly destroyed by the immune system, requiring patients to manage their blood sugar levels through intense monitoring and insulin injection. Transplantation of islets from stem cells or donor organs has allowed many patients to live without the need for insulin injections after receiving a transplant, a procedure owing in large part to the success of the "Edmonton Protocol" by Shapiro and colleagues in 2000. Currently, islet cells are infused into the liver, but it is well known that this not the ideal site or environment for the cells, and patients must be medicated with immunosuppressants for life to prevent the host's immune system from destroying the donor islets. While there has been a surge of research aimed at creating insulin-producing cells from stem cells, which could serve as an unlimited source and alleviate the burden on organ donors, the liver does not accommodate a device for housing stem cells making it not feasible for safety reasons, as these cells become irretrievable if transplanted intravenously. Using diabetic small animal models the Shapiro laboratory has recently shown the ability to maintain islet survival and reverse the diabetic state in transplanted recipients using an unprecedented discovery that allows for the modification of subcutaneous sites (below the skin). This technique, termed 'device-less' transplant, could serve to provide a preferred standard for clinical islet transplant along with other cellular therapies, helping patients to overcome their disease. Current experimental therapeutic investigation at the Shapiro laboratory includes: i)identifying an alternative site for clinical islet transplantation, ii)establishing a unlimited source of insulin-producing stem cells, and iii)the co-transplant of insulin-producing cells with other cell-types or therapies to minimize host immune responses and mitigating the need for medications