Islet xenotransplantation from genetically engineered pigs

Purpose of reviewPigs have emerged as potential sources of islets for clinical transplantation. Wild-type porcine islets (adult and neonatal) transplanted into the portal vein have successfully reversed diabetes in nonhuman primates. However, there is a rapid loss of the transplanted islets on exposure to blood, known as the instant blood-mediated inflammatory reaction (IBMIR), as well as a T-cell response that leads to rejection of the graft.Recent findingsGenetically modified pig islets offer a number of potential advantages, particularly with regard to reducing the IBMIR-related graft loss and protecting the islets from the primate immune response. Emerging data indicate that transgenes specifically targeted to pig cells using an insulin promoter (in order to maximize target tissue expression while limiting host effects) can be achieved without significant effects on the pig's glucose metabolism.SummaryExperience with the transplantation of islets from genetically engineered pigs into nonhuman primates is steadily increasing, and has involved the deletion of pig antigenic targets to reduce the primate humoral response, the expression of transgenes for human complement-regulatory and coagulation-regulatory proteins, and manipulations to reduce the effect of the T-cell response. There is increasing evidence of the advantages of using genetically engineered pigs as sources of islets for future clinical trials.