Insulin Treatment of Mice Recipients Preserves β-Cell Function in Porcine Islet Transplantation

Abstract

Encapsulation of islets of Langerhans confers protection against cell-mediated immune destruction and so should allow the transplantation of islets without immunosuppression. Xenotransplantation of encapsulated islets of Langerhans might therefore help overcome problems of human organ donor shortage. Given that islets exposed to sustained hyperglycemia show impaired β-cell function, we set out to determine whether recipient treatment with insulin could improve transplantation success rate. Islets of Langerhans were obtained from Specific Germ-Free (SPF) pig pancreas and cultured overnight. Islets were encapsulated in AN69 fibers and implanted into the peritoneal cavity of diabetic mice. A group of implanted mice was treated with exogenous insulin from day 3 to day 7 after grafting. Islet implantation depressed plasma glucose in all the mice, both insulin treated and untreated. Glycemia slowly increased in the non-insulin-treated mice, whereas the decrease observed in the insulin-treated mice was maintained until day 29 of follow-up. We found significant differences between the two groups (p < 0.05 at day 18 and day 20, p < 0.001 at day 23 and day 29). No improvement of hyperglycemia was observed in diabetic mice implanted with empty fibers. When islet-containing fibers were removed from the peritoneal cavity of mice 1 month after the graft plasma glucose increased markedly. We demonstrate that treatment of recipients with exogenous insulin in the immediate posttransplantation period has a positive effect on β-cell function in transplanted macroencapsulated porcine islets.