Human Beta Cell Proliferation In Vitro
Type 1 diabetes is characterized by the autoimmune destruction of pancreatic β-cells resulting in loss of insulin secretion, hyperglycemia, and micro- and macrovascular complications. No cure exists for type 1 diabetes and traditional therapy includes insulin replacement by multiple daily injections of subcutaneous insulin. Allogeneic islet transplantation has the potential to allow insulin independence and improve long-term outcomes in patients with type 1 diabetes. Though rates of insulin independence were initially disappointing, improvements in transplant procedures and immunosuppression regimens have lead to a significant improvement in allogeneic islet transplant outcomes. One of the factors limiting allogeneic islet transplant is the lack of islets available for transplantation. On average, at least two donor pancreases are required to harvest enough islets for one allogeneic islet cell transplantation and many patients require more than one infusion to maintain insulin independence.
Our goal is to identify methods to proliferate human islets while still maintaining their differentiated state and glucose responsiveness, in vitro. This research will lead to many indispensable outcomes that will potentially allow for one or more allogeneic islet transplants from a single donor pancreas. This project also seeks to develop protocols that can be utilized to develop a larger pool of robust, viable human islets for research purposes. By isolating human islets and culturing them in vitro we can study the effects of various growth factors, particularly TGF- β superfamily molecules, on islet proliferation, differentiation, and function.
Moving forward, we feel this work will allow us to take a targeted approach to enhance β-cell production and viability in cultured human islets. Enhancing and promoting β-cell proliferation and survival will be crucial to allow adequate tissue for islet transplant for patients suffering from type 1 diabetes. Furthermore, by promoting proliferation and viability of human β-cells and increasing the availability of this tissue, research efforts will also be enhanced.