Reduction of Immunogenicity by Cyclophosphamide Pretreatment and Culture on Xenograft Survival of Monkey Pancreatic Islets Transplanted into Rats

Introduction: Islet cell transplantation offers a new approach for the treatment of diabetes. Before transplantation, immunomodulation procedures are conducted to reduce the immunogenicity of the pancreatic islets. Aim: To study the effect of cyclophosphamide pretreatment and culture on the xenograft survival of monkey pancreatic islets. Methodology: Islets were isolated from normal monkeys and transplanted under the renal capsule of the rats. The grafts were removed 7 days after transplantation and processed for histologic study to examine graft survival. Islets from normal monkeys without cyclosporine treatment were destroyed in 7 days. These islets required cyclosporine (30 mg/kg) to prevent rejection. In the second group, the donor monkeys were treated with cyclophosphamide (60 mg/kg body weight) -4 and -2 days before harvesting of the islets. On day 0, the islets were isolated and cultured in RPMI-1640 medium for 7 days in 95% air and 5% CO 2 . After culture, the islets were transplanted into the rats. The grafts were removed and processed for histologic study to examine graft survival. Results: The pretreated and cultured islets required 15 mg/kg cyclosporine to prevent rejection. Half of the usual dose of cyclosporine is enough to prevent rejection if the donor monkeys were pretreated and the islets cultured. Conclusion: This study shows that donor pretreatment and culture reduces immunogenicity of the xenotransplanted primate islets into rats.