New Minimal Immunosuppression Strategies for Composite Tissue Allograft Transplantation: The Cleveland Clinic Experience

Abstract

Clinical application of composite tissue allografts requires the introduction of new minimal immunosuppressive or tolerance-inducing protocols. We have established a protocol for tolerance induction under α/β selective blocking antibody T-cell receptor combined with interleukin-2 blocker cyclosporin A therapy. Application of this therapy resulted in induction of tolerance in fully allogenic and semiallogenic limb allograft transplants. Based on this experience we have found that the bone marrow component of the allograft is essential for tolerance induction and have confirmed that injection of bone marrow of donor origin directly into the bone marrow compartment of allograft recipients resulted in higher chimerism levels. In addition, we have developed a system for isolation of chimeric cells, which are specific for both the donor and recipient, by using magnetic activated cell sorting technique and flow cytometry. These new, experimental approaches confirm that introducing minimal suppression to patients undergoing hand or face transplantation will likely be achieved in the near future.