Marked induction of long-term islet graft survival in gastric submucosa engrafted rats (THER5P.841)

Since the first report of successful islet transplantation to treat diabetes mellitus in rodents, selecting the optimal site for transplantation has become a key step for successful treatment. To date, the portal vein (PV) has been the primary site for clinical islet transplantation. Despite some limited success, complications, particularly instant blood-mediated inflammatory reaction (IBMIR), due to the graft site location are not conducive to long-term survival of islets and improvement of diabetes. Therefore finding a more suitable site for islet transplantation has become urgent. The gastric submucosa (GS) and kidney capsule (KC) space are fast becoming the two most common sites for islet transplantation in pre-clinical studies. Thus, these sites were compared for induction of long-term islet graft survival in rats. 24 Sprague Dawley recipients had diabetes induced by streptozocine (STZ); the STZ-induced rats were then distributed into 3 groups based on the different sites for transplantation. In our study, rats that received islets in the GS obtained better control of diabetes compared to KC and PV engrafted animals. IBMIR and pro-inflammatory cytokines also indicated an early loss of the islets in PV transplanted animals that was not evident in GS and KC animals.