The investigators have previously demonstrated that co-transplantation of syngeneic muscle cells genetically engineered to express Fas-L and pancreatic islets can prolong islet allograft survival. They now plan to extend these studies in three areas. First, they plan to test different promoters and enhancers to prolong expression of Fas-L in vivo. Second, they will test the hypothesis that pro-apoptotic signals such as Fas-L and TNF-( can be co-expressed in muscle islet composite grafts. Third, they will test whether pro-apoptotic signals can protect an islet allograft from autoimmune and alloimmune destruction in a murine model of spontaneous diabetes. Fourth, evolution of diabetes will be prevented by locally protecting islets with Fas-L.
