Arslan Emrah, Klimczak Aleksandra, Siemionow Maria
Department of Plastic Surgery, The Cleveland Clinic, Cleveland, OH 44195, USA.
Microsurgery. 2007;27(3):190-9. doi: 10.1002/micr.20330.
Composite tissue allografts (CTAs) are currently accepted in the clinic; however, long-term immunosuppression is still needed for allograft survival. The presence of donor-specific chimerism may induce tolerance. Thirty-six vascularized bone marrow transplantation (VBMT) allotransplantation were performed across MHC barrier under short-term protocol of 7-day alphabeta-TCRmAb and Cyclosporin A therapy to determine the efficacy of VBMT alone and VBMT augmented with donor bone marrow transplantation (BMT) in chimerism induction. Flow cytometry analysis revealed that VBMT supported with donor BMT directly into the bone resulted in chimerism augmentation and maintenance compared to VBMT. In vivo and in vitro tolerance testing showed prolonged survival of donor skin graft up to 35 days and moderate reactivity in MLR assay that suggests only tolerance induction. Transplantation of vascularized bone without chronic immunosuppression provides a substantial source of bone marrow cells, leading to the development of stable donor-specific chimerism.
复合组织同种异体移植(CTA)目前已被临床所接受;然而,为了同种异体移植存活仍需要长期免疫抑制。供体特异性嵌合体的存在可能诱导免疫耐受。在7天αβ-TCR单克隆抗体和环孢素A治疗的短期方案下,跨越主要组织相容性复合体(MHC)屏障进行了36例血管化骨髓移植(VBMT)同种异体移植,以确定单独VBMT以及联合供体骨髓移植(BMT)增强VBMT在嵌合体诱导中的效果。流式细胞术分析显示,与单纯VBMT相比,直接将供体BMT注入骨内支持的VBMT可导致嵌合体增加并维持。体内和体外耐受性测试表明,供体皮肤移植物存活时间延长至35天,混合淋巴细胞反应(MLR)试验中有中度反应性,这表明仅诱导了免疫耐受。无慢性免疫抑制的血管化骨移植提供了大量骨髓细胞来源,导致稳定的供体特异性嵌合体的形成。