Applications of Bilateral Vascularized Femoral Bone Marrow Transplantation for Chimerism Induction Across the Major Histocompatibility (MHC) Barrier: Part II

Bilateral vascularized bone marrow transplant (VBMT) model was designed to induce chimerism across the major histocompatibility (MHC) barrier under combined αβ T-cell receptor monoclonal antibody and cyclosporine A (αβ-TCRmAb/CsA) protocol. Seventeen transplants were performed between BN(RT1n) donors and Lewis(RTIl) recipients. Group I, isograft controls; Group II, allografts rejection controls; Group III, allografts under 7-day protocol of αβ-TCRmAb/CsA. Donor bilateral femoral bones were bilaterally anastomosed to the abdominal aorta and inferior vena cava of recipient. At day 7 posttransplantation, all bone flaps were viable. Groups I and III survived without signs of rejection. In Group III, peak level of chimerism in peripheral blood was evaluated at day 21 (24.2%), at day 63 declined to 1.5%, and was maintained at this level thereafter. Donor-derived cells were present in the bone marrow of recipients at 28.2% at day 21 posttransplant. Histology confirmed viability of bone marrow cells in isograft during the entire follow-up and up to 35 days in treatment Group III. Bilateral VBMT induced donor-specific chimerism across the MHC barrier under the immunomodulatory protocol of αβ-TCRmAb/CsA.