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% CO2. 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.