In vivo test of two low doses of mycophenolate mofetil in an experimental model of islet allotransplantation

TYPE I DIABETES MELLITUS is a major burden on patients and health-care systems. The main determinant of developing long-term complications is prolonged exposure to hyperglycemia. There is no doubt that intensive insulin regimens can reduce the onset and progression of complications from diabetes, but they are nonphysiologic and have an increased risk of causing severe hypoglycemia. In the last 30 years many medical centers worldwide have performed pancreas transplantations for the treatment of type I diabetes. This procedure has been performed in over 15,000 recipients worldwide and has an 85% rate of graft survival at 1 year. Although simultaneous pancreas–kidney transplantation has emerged as the treatment of choice for most diabetic patients with end-stage renal disease, the survival rates for patients and grafts at 5 years are over 70% and 60%, respectively. In comparison to vascularized pancreatic transplantation, islet cell transplantation can provide a minimally invasive means of restoring euglycemia and insulin-independence early in the course of diabetes. Islet cell transplantation, which avoids the surgical complications associated with vascularized pancreatic transplantation, could also improve the safety of endocrine cell replacement and reduce the cost and, consequently, increase the availability of endocrine cell replacement. Unfortunately data from the International Islet Transplant Registry have shown that only 12% of the 267 patients who received islet allografts were insulinindependent for 7 days and only 8% were insulin-independent at 1 year. Since 1995, only five centers have used mycophenolate mofetil (MMF) in combination with other immunosuppressive agents in their islet transplantation clinical protocols. In addition, in the international literature there have been few experimental reports investigating the use of MMF as an immunosuppressive treatment, most of them in models of xenotransplantation of islets. The aim of this study was to develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single immunosuppressive agent.