Abstract

Type 1 diabetes is a chronic condition where the immune system destroys insulin-producing pancreatic islet cells. Islet transplantation replaces these cells to restore blood sugar control, but faces major challenges: low cell survival, slow connection of donor islets to blood vessels, the need for repeated transplants, and limited long-term insulin independence. To overcome these limitations, we are investigating two strategies. First, we use lab-reassembled islet cell clusters called “pseudoislets”. In preclinical studies from our group and others, pseudoislets show superior survival, more efficient hormone release, and better diabetes reversal in mice compared to native islets. In this proposal, we aim to further characterize the mechanisms underlying these superior transplant outcomes. Second, we are optimizing the use of liraglutide, a medication that protects and supports insulin-producing cells. To avoid impractical, repeated injections, we developed a hydrogel that delivers liraglutide locally at the transplant site, slowly releasing the medication over time. This proposal will test this approach in diabetic mice by transplanting islet cells alongside the liraglutide-containing gel. Our study will measure cell survival, insulin restoration, blood vessel connection, and biological changes to understand the mechanisms behind any improvements. Ultimately, this research aims to advance more effective, durable islet replacement therapies. By enhancing early transplant survival and function, we hope to reduce the number of cells and procedures required for patients to achieve insulin independence, bringing us closer to a long-term cure for type 1 diabetes.