No differences in efficacy between noncultured and cultured islets in reducing hyperglycemia in a nonvascularized islet graft model

Background: Although islet transplantation is a promising method to restore normoglycemia in recipients with diabetes, large numbers of pancreatic islets are still needed. It has been suggested that the use of freshly isolated islets could improve transplantation outcome through better vascular engraftment. Using a technique of microencapsulation, a model where revascularization is not possible, we investigated the importance of revascularization for transplantation outcome. Methods: Either 700 or 350 3-day-cultured or noncultured encapsulated islets were transplanted intraperitoneally into syngeneic mice with alloxan-induced diabetes. In addition, 700 nonencapsulated islets were transplanted to mice with diabetes. Blood glucose concentrations were monitored, and glucose tolerance tests were carried out. After 42 days, the encapsulated islets were retrieved and assayed for glucose oxidation and insulin release rates. Results: There were no differences between capsules containing fresh or cultured islets in their capacity to lower the blood glucose concentration of the recipients or in the in vitro function after capsule retrieval. Interestingly, mice that were intraperitoneally transplanted with 700 encapsulated islets had average blood glucose levels well below 11 mM for most of the study, whereas the same number of nonencapsulated islets had no beneficial effects on the blood glucose homeostasis. Conclusions: Encapsulated islets can reverse hyperglycemia after transplantation to the intraperitoneal site. This effect was not seen when nonencapsulated islets were grafted. Since a 3-day culture period did not influence the outcome of transplantation of encapsulated islets there is evidence to suggest that a more appropriate revascularization may explain why freshly isolated islets are more efficient than cultured islets.