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: 2.6). 09/2009; 23(1):90-100. DOI: 10.1111/j.1432-2277.2009.00944.x
Source: PubMed


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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Available from: Mehmet Bozkurt, Nov 09, 2014
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    • "The limb represents a specific model of the VCA since vascularized bone, with bone marrow cells, constitutes a structural component of the VCA in addition to muscles, skin, nerves, and tendons. We have shown that a limb allograft contains approximately 50 × 10 6 of the bone marrow cells which may play a significant role in chimerism induction [11]. Experience with successful experimental limb transplantation across MHC-mismatched rat strains was reported by Kim et al. [12], where successful limb allograft survival was accomplished under a maintenance dose (10 mg/kg/day) of CsA monotherapy. "
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    ABSTRACT: The preclinical experimental models of vascularized composite allografts (VCAs) have been rapidly developed for the assessment of immunomodulatory protocols for clinical application. Recently, researchers have focused on immunomodulatory protocols which overcome the immunologic barrier between the allogeneic donor and recipient and may lead to tolerance induction. In order to test the feasibility of chimerism induction, experimental VCAs have been performed in different models including rodents, large animals, and nonhuman primates. These models differ in the complexity of transplanted tissue and in their responses to immunomodulatory protocols. In most applications, VCA contains multiple-tissue components; however, each individual component of CTA possesses unique immunologic characteristics that ultimately contribute to the chimerism induction and successful outcome of the VCA. Heterogenic character and complexity of tissue components in different VCA models determine the quality and robustness of donor-specific chimerism. As introduced in experimental studies, variable immunomodulatory options have been studied to achieve tolerance to VCA in rodents and large animal models allowing for widespread application in clinic. In this paper, based on our own experience, we have analyzed the current knowledge of tolerance-inducing strategies via chimerism induction in VCA experimental models in the context of immunomodulatory protocols and VCA complexity and their relevance and applicability to clinical practice.
    Full-text · Article · Mar 2013 · Clinical and Developmental Immunology
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    • "This model promotes long-term mixed chimerism and tolerance [74] with a decreased incidence of GVHD [75]. The sources of the vascularized bones tested have been hind limb [76, 77], sternum [78], femur [79], maxilla [80], and ilium [81]. "
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    ABSTRACT: Successful hand and face transplantation in the last decade has firmly established the field of vascularized composite allotransplantation (VCA). The experience in VCA has thus far been very similar to solid organ transplantation in terms of the morbidity associated with long-term immunosuppression. The unique immunological features of VCA such as split tolerance and resistance to chronic rejection are being investigated. Simultaneously there has been laboratory work studying tolerogenic protocols in animal VCA models. In order to optimize VCA outcomes, translational studies are needed to develop less toxic immunosuppression and possibly achieve donor-specific tolerance. This article reviews the immunology, animal models, mixed chimerism & tolerance induction in VCA and the direction of future research to enable better understanding and wider application of VCA.
    Full-text · Article · Oct 2012 · Clinical and Developmental Immunology
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    ABSTRACT: In this study, we extended application of face transplantation model in rat by incorporation of vascularized premaxilla, and nose with infraorbital and facial nerves for evaluation of allotransplanted sensory and motor nerve functional recovery. In group I (n = 3) the dissection technique is studied. In group II (n = 5) isotransplantations were performed. In group III (n = 5) allotransplantations were performed under Cyclosporin A monotherapy. Grafts; composed of nose, lower lip, and premaxilla; were dissected. Infraorbital nerve and facial nerve were included into the transplant. A heterotopic transplantation was performed to inguinal region of recipient. Nerve coaptations were performed between infraorbital-sapheneous nerve and facial-femoral nerve. CT scan, somatosensory-evoked potential testing (SSEP), motor-evoked potential testing (MEP), and microangiography were used for evaluation. All transplants survived indefinitely over 100 days. Microangiography showed preserved vascularization of the graft. Computed tomography revealed vital premaxillary bone segments. SSEP and MEP confirmed recovery of motor and sensory functions and latencies reached 67% of normal infraorbital nerve value and 70% of normal facial nerve value at 100 days post-transplant. We have introduced new midface transplant model of composite midface allograft with sensory and motor units. In this model, motor and sensory functional recovery was confirmed at 100 days post-transplant.
    Full-text · Article · Dec 2009 · Transplant International
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