The intraperitoneal injection of insulin-producing islets, immunoprotected by an alginate-polyamino acid membrane, is a potential method of reversing diabetes without the need for life-long immunosuppression. Using alginate high in guluronic acid content, we have successfully reversed diabetes in the spontaneous &abetic dog model followinz intraDeritoneal (IP) encapsulated allograft. Two-year follow-up studies in five dogs successfully treated with encapsulated islets demonstrated that multiple transplants were safe and efficacious with excellent long-term glycemic control and ongoing graft function even after discontinuation of all antirejection drugs. Toxicity studies of the capsule demonstrated no evidence of acute toxicitY or mutagenicity. These studies formed the preclinical basis for human clinical trials. We have completed our first human clinical transplant of encapsulated islets in a Type I diabetic patient and have demonstrated ongoing islet function over six months post transplant. In order for this technology to be made available to the I . I million diabetic patients who could benefit from this procedure xenograft encapsulated islets must be developed. We will develop islet isolation techniques from pig pancreata utilizing collagenase developed by recombination DNA technology, and demonstrating that encapsulated porcine islets can reverse diabetes in the small animal model.Awardee's statement of the otential commercial applications of the research: Twelve million Americans suffer from diabetes, of which 10% are insulin-dependent. Despite insulin therapy, these patients suffer from severe complications of the disease. Diabetes remains the 3rd leadin$ cause of death in the USA and the cost to our country is estimated at $20 billion per year. If encapsulated porcine Islets could be perfected as a bioartificial pancreas, the potential exists that millions of patients could benefit from this procedure.National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
