Grant: Operating Grant

Advances in transplantation of human islets have established the proof-of-concept for this therapy to emerge as a treatment for patients with Type 1 diabetes. Despite efforts to maximize organ donation the number of human islets available for transplantation continues to limit the number of patients who can be transplanted. One approach to address this rate-limiting problem is to use islets from an animal source such as pigs. This proposal seeks to advance the possibility of pig islet transplantation, since: 1) porcine insulin has been used to treat diabetes for more than 60 years; 2) porcine islets respond to glucose in the same manner as do human islets; 3) pigs breed rapidly and produce large litters, providing a virtually unlimited source of islets; and moreover 4) our group has shown that Neonatal Porcine Islets (NPIs) are able to correct diabetes in the preclinical non-human primate model. We believe that in the near future NPIs will be used for clinical transplantation for patients with Type 1 diabetes and thereby solve the shortage of insulin-producing tissue. Principal challenges that must be met to make transplantation of NPIs a clinical reality include: 1) defining a reproducible strategy for isolating large numbers of clinically grade NPIs; and 2) to develop a means of transplanting NPIs without the need for life-long anti-rejection drugs. Therefore, the objectives of the research proposal are to: 1) To characterize NPIs isolated from wild type and genetically modified pigs obtained from a closed herd. 2) To develop Good Manufacturing Practice (GMP) compliant and clinically scale-able protocols for the preparation of clinical grade NPI grafts. 3) To develop a clinically applicable site to implant NPI grafts in a pancreatectomized pre-clinical large animal model. We believe that these studies will facilitate and expedite clinical trials of neonatal porcine islets thereby allowing the treatment of many more patients with Type 1 diabetes.