Nonhuman primate models of islet transplantation: preclinical testing of novel immunotherapies

Studies in rodent models pro,ide key insights into the pathways that regula te immune responses to foreign antigens, including transplanted tissues. In addition, spontaneous and induced models of autoimmunity in these species allow for dissection of cellular and molecular routes to disease. Translati on of the results to larger animal models (e.g., nonhuman primates) and hum ans, however, is rarely straightforward. Clinically; islet cell transplanta tion has resulted in reversal of hyperglycemia and normalization of metabol ic control, without the occurrence of hypoglycemia, in a limited number of patients, The immunosuppressive agents that work well for solid organ trans plantation only rarely lead to insulin independence and long-term islet all ograft survival, The reasons for this disappointing success rate include re jection, recurrence of autoimmunity, early islet loss as a consequence of n onspecific inflammatory events that occur upon intrahepatic islet transplan tation, and the adverse effects of conventional immunosuppressive drugs on islet cell function. The introduction of novel immunomodulatory agents has, for the first time, recently led to advances in our ability to consistentl y prevent rejection and allow for long-term insulin independence in nonhuma n primates.