Grant: CIHR Fellowship

Type 1 diabetes mellitus (T1D) is an autoimmune disease where the patient's immune system destroys pancreatic islets, resulting in lack of insulin. Islet cell transplantation can reverse diabetes and patients are able to discontinue insulin injections; however, up to 60% of the islets die after transplantation and hence, multiple donors per recipient are required. Protecting the transplanted islets from death is critical. In addition, the autoimmunity associated to T1D results in the destruction of the new islets and patients must often return to insulin administration. Due to donor limitations and the requirement of immunosuppression, islet transplantation is only available to 10% of the population suffering from T1D. With this proposal, we aim to overcome current clinical hurdles facing islet transplantation by employing two graft localized therapeutic delivery systems composed of a biomaterial, PLGA, to enhance islet graft survival and function when transplanted under the skin. First, we will use a retrievable subcutaneous bio-active scaffold that will provide structural support to the transplanted islets and create an environment that facilitates their optimal functioning. By utilizing this scaffold, we aim to enhance the survival rate of the islet grafts and promote their integration into the surrounding tissue. Next, we will use islet graft localized PLGA drug eluting microparticles, which release therapeutic substances in a controlled manner, targeting key factors that influence the success of islet transplantation. By evaluating the impact of this drug eluting system on post-transplant immune modulation, insulin secretion, and cell death, we seek to augment the engraftment of islets and improve overall transplantation outcomes. Combining these approaches we hypothesize that we can establish a highly vascularized and optimal space within the skin that will allow the survival and long-term function of the islets without the need of immunosuppression.