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.

Feasibility of cryopreserved tracheal xenotransplants with the use of short-course immunosuppression

“…14,15 Valdivia and associates 16 reported FK506 to potentially suppress antibody production in hamster-torat xenotransplantation. Hebebrand and colleagues 17 showed FK506 to be a better immunosuppressive agent than RS61443, which they expected for xenograft survival because of its mechanism of action to reduce natural antibodies. For these reasons, we also selected FK506 alone as an immunosuppressant in these experiments.…”

Xenotransplantation model for vascularized musculoskeletal tissues in rodents

“…3,4 Whereas transplantation of xenogeneic visceral organs has been widely studied, vascularized musculoskeletal xenografts have only recently been investigated in a hamster-to-rat model. 5 The wide commercial availability of mouse and rat antibodies to various immune complex proteins and cell surface markers makes these strain combinations highly suitable for studying vascularized xenotransplantation. The goals of this study, therefore, were to determine immunologic baseline data between mice and rats using skin grafting and to establish a vascularized musculoskeletal xenotransplantation model between mice and rats.…”

Literature update 1998, part 2

“…Studies of cell-mediated xenograft rejection continued to emphasize the basic similarities of in vitro T cell-mediated human-anti-pig and human allogeneic responses [33,34]. In vivo, however, especially vigorous immunosuppression is still required for xenografts [35]. In a pig-to-mouse combination, combined co-stimulatory blockade was remarkably effective in prolonging graft survival [36], suggesting again that in this particular species combination there may be molecular incompatibilities that weaken some aspects of cell-mediated rejection.…”