EFFECT OF CYCLOSPORIN-A AS AN IMMUNOSUPPRESSIVE DRUG ON ISLET CELLS TRANSPLANTATION IN MICE

Abstract

Transplantation of normal isolated islets of langerhans for the treatment of diabetes remains an elusive goal in clinical practice. Perhaps the major problem preventing clinical islet transplantation has been limited by the inability to prevent islet allograft or xenograft rejection. Cyclosporin A is an immunosuppressive agent that improves survival of transplant. This exciting immunosuppressive agent was first used clinically in renal transplantation in 1978 (Ferguson and Fidlus 1982).The aim of this study was the isolation , purification and transplantation of hamster pancreatic islet as xenograft transplantation for the treatment of diabetic mice. It is also aimed to study the effect of cyclosporin A as an immunosuppressive agent on some biochemical parameters e.g blood glucose and blood insulin levels to induce maximum suppression of mice immune system and consequently realizing maximum survival of transplanted islets. A total of 30 streptozotocin induced mice were randomized to receive islets xenografts from golden syrian hamsters by three different approaches ,the first group of ten mice received islets only in the renal subcapsular space, the 2nd of ten mice received islets in the renal subcapsular space and was given cyclosporin A in a dose of 15 mg/kg/day for three days.The 3rd group of ten mice were received islets in the renal subcapsular space and were given cyclosporin A orally every day at a dose of 15 mg/kg/day for three days which was gradually decreased to 5 mg/kg/day. Non of the mice of group 1 became normoglycemic. All mice of group 2 became normoglycemic for 11±4 ( range 6-18 days) . only mice of group 3 enjoyed normoglycemic as long as cyclosporin-A was administrated. Consequantly, prolonged survival of islets xenografts may be achieved with administration of cyclosporin-A.