New composite tissue allograft model of vascularized bone marrow transplant: the iliac osteomyocutaneous flap.

Department of Plastic and Reconstructive Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
Transplant International (Impact Factor: 3.16). 09/2009; 23(1):90-100. DOI: 10.1111/j.1432-2277.2009.00944.x
Source: PubMed

ABSTRACT Vascularized bone marrow transplant (VBMT) induces donor-specific chimerism in experimental models across the major histocompatibility barrier. An experimental model for immunotolerance studies should sustain a high antigenicity with low morbidity. Accordingly, we introduced an iliac bone osteomusculocutaneous (IBOMC) transplant model in rat. It consists of a large skin component and an abundant bone marrow cells (BMC) population. We tested this model with isograft transplantations between Lewis rats (RT1(l)) and with allograft transplantation between Lewis-Brown Norway (LBN RT1(l + n)) donors and Lewis (RT1(l)) recipients under low dose of cyclosporine A monotherapy. Immunologic responses were tested for donor cell engraftment and chimerism induction. All isografts survived indefinitely and allografts were viable at 200 days post-transplant under low dose of cyclosporine A. Microangiography of the graft revealed preservation of skin, muscle, and bone components. Histologic examination confirmed viability of all allograft components without signs of rejection. Long-term engraftment of donor-origin (RT1(n)) BMC was confirmed by donor-specific chimerism (1.2%) in peripheral blood and bone marrow (1.65%) compartments and by engraftment into lymphoid organs of recipients. The IBOMC transplant proved to be a reliable composite tissue allotransplantation (CTA) model. Moreover, because of its robust bone marrow component and large skin component, it is applicable to studies on immunologic responses in CTA.

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    ABSTRACT: Vascularized bone marrow transplantation (VBMT) appears to promote tolerance for vascularized composite allotransplantation (VCA). However, it is unclear whether VBMT is critical for tolerance induction and, if so, whether there is a finite amount of VCA that VBMT can support. We investigated this with a novel VCA combined flap model incorporating full thickness hemiabdominal wall and hindlimb osteomyocutaneous (HAW/HLOMC) flaps. Effects of allograft mass (AM) and VBMT on VCA outcome were studied by comparing HAW/HLOMC VCAs with fully MHC-mismatched BN donors and Lewis recipients. Control groups did not receive treatments following transplantation. Treatment groups received a short course of cyclosporine A (CsA), anti-lymphocyte serum and three doses of adipocyte-derived stem cells (POD 1, 8 and 15). The results showed that all flaps in control allogeneic groups rejected soon after VCAs. Treatment significantly prolonged allograft survival. Three of eight recipients in HLOMC treatment group had allografts survive long-term and developed donor-specific tolerance. Significantly higher peripheral chimerism was observed in HLOMC than other groups. It is concluded that the relative amount of AM to VBMT is a critical factor influencing long-term allograft survival. Accordingly, VBMT content compared to VCA mass may be an important consideration for VCA in humans.This article is protected by copyright. All rights reserved.
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