Tolerance induction following allogeneic vascularized bone marrow transplantation — the possible role of microchimerism

Abstract

We have noticed that bone marrow transplanted in a vascularized limb graft, providing a continuous supply of donor bone marrow cells (BMC), may prolong the survival time of a skin graft from the same donor. The question arises whether the microchimerism raised plays a role in the prolonged survival of skin allografts. The aim of the study was to follow the development of microchimerism after allogeneic vascularized bone marrow transplantation (VBMTx) concomitantly with the rejection process of transplanted skin. Brown Norway (BN) rats served as donors and Lewis rats as recipients of VBMTx and free skin flap allografts. A hind limb was transplanted, followed by a full-thickness skin graft on the dorsum. Cellular microchimerism was investigated in recipients of VBMTx and skin grafts in blood, spleen, mesenteric lymph node, and bone marrow with the monoclonal antibody OX27 directed against MHC class I polymorphic RT1 on BN cells and quantitatively analyzed in a FACStar. In the VBMTx group, the free skin flap survived 70 days after weaning off cyclosporine A (CsA). An intravenous infusion of BMC in suspension equivalent to that grafted in the hind limb did not prolong skin graft survival after cessation of CsA therapy. Donor-derived cells could be detected in VBMTx recipients as long 70 days after weaning off CsA but not in recipients of i.v. suspension BMC grafting.

Review of vascularized bone marrow transplantation: Current status and future clinical applications

“…In contrast, a VBMT graft bypasses the engraftment period by providing its own stromal environment, and is therefore capable of immediate cellular expansion. Janczewska and coworkers 8,33 studied immune reconstitution in hind-limb allografts (VBMT) and found that lethally irradiated recipient rats (8 Gy) demonstrated rapid immune reconstitution in both syngeneic and allogeneic VBMT models when compared with cellular BMT controls.…”