Islet cell transplantation: In vivo and in vitro functional assessment of nonhuman primate pancreatic islets

Transplantation of pancreatic islets of Langerhans as a therapeutic approac h for treatment of type I diabetes offers an alternative to subcutaneous in sulin injections. Normalization of blood glucose levels by transplanted isl ets may prevent, the development of diabetes-related complications. Problem s related to rejection, recurrence of autoimmunity, and local inflammation upon transplantation of islets into the liver need to be solved before the implementation of islet cell transplantation can be viewed as a justifiable procedure in a large cohort of patients. Islet cell isolation has been qui te successful in small animals, but the translation of this approach to non human primates has been less rewarding. One of the main problems encountere d in nonhuman primate models is the difficulty of isolating an adequate num ber of functional islets for transplantation. The aim of the present study was to develop a method for isolating a sufficient number of viable islets from nonhuman primates to allow for reversal of diabetes. By implementing m inor modifications in the automated method for human islet isolation we wer e able to obtain viable, functional islets that responded normally to gluco se stimulation in vitro. These islets were also able to reverse diabetes in immunocompromised nude mice, rendered diabetic by streptozotocin. This met hod of islet cell isolation has enabled us to proceed with protocols of all ogeneic islet cell transplantation in preclinical, nonhuman primate models.