Limb Xenotransplantation Using FK506 and RS61443 Immunosuppression

ABSTRACT

A new model of limb xenotransplantation has been developed to determine whether the newer immunosuppressive agents, FK-506 and RS-61443, either alone or in combination, can delay the rejection of a composite limb xenograft from donor Golden Syrian hamsters to recipient Lewis rats. Using a short-term course of immunosuppression for 14 days post-transplant, both FK-506 2 mg/kg/day and RS-61443 30 mg/kg/day were able to delay rejection. FK-506-treated animals had a mean rejection time of 10.2 days and RS-61443-treated animals had a mean rejection time of 10 days, compared with a mean rejection time of 6.4 days in non-immunosuppressed controls. Combination and sequential immunosuppression with both FK-506 and RS-61443 did not produce any improvement, compared with single-agent immunosuppression, and were quite toxic. Histologically, FK-506 seemed to prevent signs of rejection in the skin and muscle components of the limb xenograft better than RS-61443.