| The discrepancy between the consistent success of whole organ pancreas transplants and the anecdotal success of isolated pancreatic islet transplants to cure type 1 diabetic patients has been attributed to technical factors (islet preparation from the whole organ), and immunologic factors. Since allogeneic islets within an intact pancreas are not rejected in humans with current immunosuppression, technical factors must be critical. The objectives were to improve the success rate of islet autotransplants in a preclinical model by alternative techniques, and to define the natural history of islet autografts in pancreatectomized human beings.;The islet isolation and transplant procedures were simplified by eliminating the purification step and by using the peritoneal cavity as an alternative implantation site. Also, posttransplant glycemic control was established in the diabetic recipient to provide initial metabolic "rest" for the transplanted islets. These changes were hypothesized to improve the metabolic function of transplanted islets by increasing the number of islets that survive posttransplant. In a diabetic canine model, impure islet autografts implanted in the peritoneal cavity had a higher rate of insulin independence, and better preserved metabolic function with compared with pure islets implanted in the liver. Glycemic control in the diabetic recipient after islet transplant was not deleterious, and improved the early success rate of a subset of islet autografts that uniformly failed without insulin therapy.;The natural history of intrahepatic impure islet autotransplants after total pancreatectomy in humans was hypothesized to be dependent on the number of islets transplanted and technique of islet preparation. The results in 48 patients supported this hypothesis; 74% of patients who received more than 300,000 islets remained insulin independent, compared with 10% of patients who received less this number. The number of islets recovered from the pancreases was related to technical factors: (1) the pancreas dispersion method; and (2) the morphology of the pancreas.;These data are consistent with the hypotheses that simplifying the islet isolation and transplant procedure improves the rate of insulin independence and metabolic function of islet autografts in dogs, and that the number of islets transplanted, and not islet purity, is critical for success in humans. |
