Xenografts - One of the limitations of an islet cell transplant program is the availability of human islet cells. An alternative to human islets is islets from animal sources. One excellent source is pig islets because porcine insulin is nearly identical to human insulin. A goal of the ICTU will be to perfect porcine islet harvest and long-term cryostorage. One strategy to prevent islet cell rejection is microencapsulation of islet cells. In this approach, islet cells are coated with a protective membrane that allows for the secretion of insulin, but protects the cell against antibodies and other cytokines involved in rejection. Alternative sites for transplantation - One of the problems of transplantation is to find an ideal site for placement of transplanted islet cells. Ideally, islet cells should be implanted in sites proximal to the portal circulation, as this resembles physiologic conditions. However, alternative sites may afford greater protection against rejection. The ICTU researchers will attempt transplantation at other sites including the bone marrow in animal models to determine whether there is an advantage to other sites in terms of both immune-protection and preservation of islet cells. Immune-protection - The ultimate success of islet cell transplantation depends on preventing islet cell rejection and a resumption of the autoimmune attack directed towards the transplanted islet cells. Despite poor results in the past, recent progress in encapsulating material promises exciting development in this area in the near future. With the use of animal models, ICTU immunologists will attempt to develop improved immunosuppressive regimens that maximize synergy between different immunosuppressive agents. Immunosuppressive protocols will be initially done in animals which will allow for examination of transplanted islet cells and other organs to determine the degree of immune-suppression and side effects. Function of transplanted islet cells - A major issue is whether transplanted islets offer advantages over conventional therapy in terms of improved metabolic control and prevention of long-term complications. Animal models will be used to determine whether glucose control is restored to normal in transplanted diabetic animals, and whether long-term complications are prevented. The data from these experiments will help in determining whether islet cell transplants is cost-effective and a viable alternative to conventional therapy.