Effects of mycophenolate mofetilvscyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

Abstract

To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C received mycophenolate mofetil (MMF) (20 mg/kg). The animals were killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P<0.01). No difference in allograft survival between the CsA and MMF groups was found. However, MMF had less renal and hepatic toxicity and allowed weight gain. Monotherapy with MMF for immunosuppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.