Pancreatic islet cell transplantation: past, present and future.

Experimental islet cell transplantation is very successful. In syngeneic strains of rodents isolated and purified islets from multiple donors infused into the portal vein of a diabetic recipient can normalize glucose and prevent microvascular complications. The techniques used to isolate and purify islets in rodents could not be adapted to the fibrous mammalian pancreas. It was not possible to harvest a sufficient volume of isolated islets from one pancreas to restore metabolic function in a diabetic recipient. A partial solution to the problem was to eliminate the steps of purification used in rodents and transplant dispersed pancreatic fragments consisting of islet cells as well as contaminating exocrine, endothelial, ductal and specific immune cells. Initial clinical trials using impure pancreatic fragment grafts were unsuccessful and risky dampening enthusiasm for islet transplantation in general. It was during this same time period that Lacy and Lafferty demonstrated that deletion of donor immune cells from a graft preparation of isolated islets in rodents prolonged allograft survival without immunosuppression. This exciting discovery revived efforts to isolate high yields of pure islets from the mammalian pancreas. The major objective of experimental studies at present is directed at finding a practical and efficient means of separating the endocrine component of the pancreas from contaminating exocrine and immunogenic cells. Escalating success in this area has permitted clinical trials of islet transplantation to resume with optimism for success.