Bilateral vascularized composite skin/bone transplantation models

Abstract

It is important to understand the mechanisms of bone marrow based allograft tolerance induction to explain the diverse variables controlling the subsequent outcome of the solid organ and composite tissue allotransplants. To be able to introduce bone marrow transplantation as a routine clinical application, further experimental studies are needed to overcome the problems related to the bone marrow transplantation, including graft versus host disease, immunocompetance, and toxicity of the conditioning regimens. Therefore alternative experimental models are needed. In this study, we introduced different experimental models of modified vascularized skin/bone marrow transplantation technique for tolerance induction, monitoring and maintenance; to be able to provide a reliable research tool for bone marrow based tolerance induction experiments. We investigated the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants in this model. Bilateral skin/bone transplantation model may allow to study new strategies in tolerance induction by modifying the amount of the immunogenic load in the form of skin transplant and by altering the amount of vascularized bone marrow delivery in the form of vascularized bone transplantation allowing for accelerated engraftment of stem and progenitor cells.