Achieving Tolerance in a Mismatched VCA Transplant While Reducing the Risk of GVHD: The Goal of Transient Chimerism

BACKGROUND: Transplantation of vascularized composite allografts (VCA) offers the opportunity to restore form and function. Clinical application is limited due to the necessity of life-long immunosuppression. One promising method of inducing tolerance to an organ allograft is the development of mixed chimerism. We have demonstrated that a nonmyeloablative stem cell transplant can lead to tolerance in a mismatched dog model. However, the application of this protocol has been limited by graft-versus-host disease (GVHD). We have observed several animals that, after an initial period of donor cell engraftment, lost their stem cell allograft but remained tolerant to the VCA. Conversely, animals that retained persistent donor cell chimerism inevitably developed GVHD. The hypothesis for this study was that our non-myeloablative hematopoietic stem cell transplant protocol could be used to induce tolerance to a recipient VCA without the need for persistent donor cell chimerism.