Encapsulated Porcine Islets as a Bioartificial Pancreas

The intraperitoneal injection of insulin-producing islets, immunoprotected by an alginate-polyam-ino acid membrane, is a potential method of reversing diabetes without the need for life-longimmunosuppression. Using alginate high in guluronic acid content, we have successfully reverseddiabetes in the spontaneous diabetic dog model following intraperitoneal (IP) encapsulated allograft.Two-year follow-up studies in five dogs successfully treated with encapsulated islets demonstrated thatmultiple transplants were safe and efficacious with excellent long-term glycemic control and ongoinggraft function even after discontinuation of all antirejection drugs. Toxicity studies of the capsuledemonstrated no evidence of acute toxicity or mutagenicity. These studies formed the preclinical basisfor human clinical trials. We have completed our first human clinical transplant of encapsulated isletsin a Type I diabetic patient and have demonstrated ongoing islet function over six months posttransplant. In order for this technology to be made available to the 1.1 million diabetic patients whocould benefit from this procedure xenograft encapsulated islets must be developed. We will develop isletisolation techniques from pig pancreata utilizing collagenase developed by recombination DNAtechnology, and demonstrating that encapsulated porcine islets can reverse diabetes in the small animalmodel.