PORCINE PANCREATIC-ISLETS - ISOLATION, MICROENCAPSULATION, AND XENOTRANSPLANTATION

To provide a plentiful source of pancreatic islets for future clinical transplants into diabetic patients, we have developed a simple and re liable method to isolate porcine islets of a high degree of purity. Po rcine pancreata were perfused and digested with collagenase, and the i slets were then purified on dextran density gradients. In order to avo id any damage to the islets, no mechanical devices nor any strenuous t reatment was employed. As many as 5 x 10(5) islets were isolated from a single porcine pancreas. Islets were encapsulated in alginate-polyly sine-alginate membranes with the aid of an electrostatic droplet gener ator. In vitro studies demonstrated that the isolated islets secreted insulin in response to glucose and 3-isobutyl-L-methylxanthine (IBMX) challenge for at least 4 weeks. Perifusion studies showed that the kin etics of insulin release from the encapsulated islets was similar to t hat exhibited by free islets. In in vivo studies, 18 diabetic BALBc mi ce were transplanted with 1,500-2,500 encapsulated islets each. In 13 recipients, the diabetic condition was reversed for at least 85 days. When capsules were removed from 2 transplant recipients, their diabeti c condition quickly recurred.