Cetrulo Curtis L, Drijkoningen Tessa, Sachs David H
aVascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA bDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA cTransplantation Biology Research Center Laboratories, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA.
Curr Opin Organ Transplant. 2015 Dec;20(6):602-7. doi: 10.1097/MOT.0000000000000248.
The present review summarizes current data on the induction of immunologic tolerance through mixed hematopoietic chimerism relevant to applying this approach to vascularized composite allotransplantation.
Clinical allograft tolerance has been achieved recently for kidney transplants, using nonmyeloablative conditioning regimens and bone marrow transplantation from living donors. The mixed chimerism attained in these studies was either transient or durable, and both permitted tolerance of the renal allografts to be achieved across MHC-matched and MHC-mismatched barriers. In order to extend these protocols to deceased donor transplants across full MHC-mismatched combinations, as will be required for vascularized composite allografts (VCA), a delayed tolerance protocol has recently been developed, in which the donor bone marrow is given 4 months posttransplant. Recent primate studies of kidney transplants using this protocol have been successful and have demonstrated that strategies to abrogate memory T cells may be helpful.
Induction of tolerance in renal allograft transplantation has been achieved clinically, via mixed chimerism protocols. Modifications of these protocols for transplants, which require use of deceased donors across full MHC mismatches, have shown promise in preclinical models. It is therefore appropriate to consider evaluation of these protocols in clinical trials for kidney transplants, and if successful, for VCA.
本综述总结了通过混合造血嵌合体诱导免疫耐受的当前数据,这些数据与将该方法应用于血管化复合组织同种异体移植相关。
最近,通过使用非清髓性预处理方案和活体供者的骨髓移植,肾移植已实现临床同种异体移植耐受。这些研究中获得的混合嵌合体要么是短暂的,要么是持久的,二者均能使肾同种异体移植跨越MHC匹配和MHC不匹配的障碍而实现耐受。为了将这些方案扩展到全MHC不匹配组合的 deceased 供者移植,这是血管化复合组织异体移植(VCA)所需要的,最近开发了一种延迟耐受方案,即在移植后4个月给予供者骨髓。最近使用该方案对肾移植进行的灵长类动物研究取得了成功,并表明消除记忆T细胞的策略可能会有所帮助。
通过混合嵌合体方案,肾同种异体移植临床上已实现耐受诱导。针对需要使用全MHC不匹配的 deceased 供者进行移植的这些方案的修改,在临床前模型中已显示出前景。因此,考虑在肾移植的临床试验中评估这些方案是合适的,如果成功,则可用于VCA。