造血干细胞输注/移植以诱导同种异体移植耐受。
Hematopoietic stem cell infusion/transplantation for induction of allograft tolerance.
作者信息
Granados Jose M M, Benichou Gilles, Kawai Tatsuo
机构信息
Department of Surgery, Massachusetts General Hospital, Center for Transplantation Sciences, Harvard Medical School, Boston, Massachusetts, USA.
出版信息
Curr Opin Organ Transplant. 2015 Feb;20(1):49-56. doi: 10.1097/MOT.0000000000000159.
PURPOSE OF REVIEW
The present review updates the current status of basic, preclinical, and clinical research on donor hematopoietic stem cell infusion for allograft tolerance induction.
RECENT FINDINGS
Recent basic studies in mice provide evidence of significant involvement of both central deletional and peripheral regulatory mechanisms in induction and maintenance of allograft tolerance effected through a mixed chimerism approach with donor hematopoietic stem cell infusion. The presence of heterologous memory T cells in primates hampers the induction of persistent chimerism. Durable mixed chimerism, however, now has been recently induced in inbred major histocompatibility complex-mismatched swine, resulting in tolerance of vascularized composite tissue allografts. In clinical transplantation, allograft tolerance has been achieved in human leukocyte antigen-mismatched kidney transplantation after the induction of transient mixed chimerism or persistent full donor chimerism.
SUMMARY
Tolerance induction in clinical kidney transplantation has been achieved by donor hematopoietic stem cell infusion. Improving the consistency and safety of tolerance induction and extending successful protocols to other organs, and to organs from deceased donors, are critical next steps to bringing tolerance to a wider range of clinical applications.
综述目的
本综述更新了关于供体造血干细胞输注诱导同种异体移植耐受的基础、临床前和临床研究的现状。
最新发现
近期在小鼠身上进行的基础研究表明,通过供体造血干细胞输注的混合嵌合体方法诱导和维持同种异体移植耐受过程中,中枢性删除和外周调节机制均有显著参与。灵长类动物中异源记忆T细胞的存在阻碍了持续性嵌合体的诱导。然而,最近在近交系主要组织相容性复合体不匹配的猪中诱导出了持久的混合嵌合体,从而实现了对血管化复合组织同种异体移植的耐受。在临床移植中,诱导短暂混合嵌合体或持久的完全供体嵌合体后,在人类白细胞抗原不匹配的肾移植中实现了同种异体移植耐受。
总结
通过供体造血干细胞输注已在临床肾移植中实现了耐受诱导。提高耐受诱导的一致性和安全性,并将成功方案扩展到其他器官以及来自 deceased 供体的器官,是将耐受应用于更广泛临床领域的关键下一步。 (注:deceased 未找到合适中文对应词,保留英文)