Neonatal Porcine Islets as a Possible Source of Tissue for Humans and Microencapsulation Improves the Metabolic Response of Islet Graft Posttransplantation

Current methods for treating insulin-dependent (Type 1) diabetes mellitus do not prevent transient episodes of hyperglycemia.' Recurrent hyperglycemia has been suggested to cause chronic lesions which can culminate in renal failure, blindness, heart disease, neuropathy, or atherosclerosis.* Recently the Diabetes Control and Complications Trial demonstrated that long-term intensive insulin treatment was associated with a reduced risk of developing diabetes-related complications? This intensive therapy, however, can result in harmful side effects due to recurrent hypoglycemia, and the extraordinary effort required in self-monitoring and in providing ongoing management for these patients may exceed the capabilities of many individuals and their health care providers. An attractive alternative is to transplant insulin-producing tissue, which can offer a more physiological approach for precise restoration of glucose homeostasis, thereby reversing the metabolic and neurovascular complications of diabetes. Compared to vascularized pancreatic grafts, transplantation of isolated islets offers a number of advantages. For example, donor islet tissue can be tested andor pretreated before implantation, thus allowing the possibility of using grafts with defined metabolic or immunological characteristics. Since 1974,236 adult human islet allografts have been performed in European and North American centers! A detailed analysis of 75 type 1 diabetics (C-peptide negative) transplanted with adult islet allografts from 1990 to 1993 showed a 1 year patient survival of 95% and a graft survival (defined by basal C-peptide >1 ng/ml) of only 28%.5 Eight of these patients were insulin independent for >1 year, of which two were from our program in Edmonton.6.' Insulin independence in these