Vascularized bone marrow transplantation: A new surgical approach using isolated femoral bone/bone marrow

Background. Orthotopic composite tissue (limb) transplantation in rats is a unique model for vascularized bone marrow transplantation because bone mar row cells and bone marrow stroma are transplanted by microsurgical means, t hus creating immediate bone marrow space and engraftment. However, it conta ins a skin component and other musculoskeletal tissues that complicate issu es related to tolerance induction. Materials and methods. To study only aspects of vascularized bone marrow tr ansplantation, we created a new isolated vascularized bone marrow transplan t model in rats. The common iliac (or femoral) artery and vein were microsu rgically anastomosed to the recipient abdominal aorta and inferior vena cav a in an end-to-side fashion, respectively, Syngeneic male Lewis (RT1(1), n = 20) and allogeneic male BN (RT1(n), n = 10) donors were transplanted to f emale Lewis recipients. To establish rejection criteria, we examined histop athology and used the polymerase chain reaction (PCR) to assess microchimer ism of donor male bone marrow cells in the peripheral blood of female recip ients using rat Y chromosome (sex-determining region Y)-specific primers. Results. All recipients were healthy and remained stable without major comp lications for up to 300 days posttransplant, Morphologically, syngeneic mal e Lewis bone marrow showed a near-normal appearance. Allogeneic male BN bon e marrow was clearly rejected, Male bone marrow cells were detected by PCR in the peripheral blood of all syngeneic recipients, but not in allogeneic blood specimens. Conclusions. A new surgical approach to bone marrow transplantation was est ablished. This consisted of the vascularized femoral bone/bone marrow trans plant, Further analyses regarding the ability of vascularized femoral bone marrow transplants to induce systemic transplantation tolerance in adult ra ts will provide insights into not only various issues of immunology but als o the potential clinical application of vascularized bone marrow transplant ation. (C) 2000 Academic Press.