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间充质基质细胞促进实体器官移植耐受。

Mesenchymal stromal cells to promote solid organ transplantation tolerance.

机构信息

Department of Immunology and Transplantation, Transplant Research Center Chiara Cucchi de Alessandri e Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Ospedali Riuniti - Mario Negri Institute for Pharmacological Research, Bergamo, Italy.

出版信息

Curr Opin Organ Transplant. 2013 Feb;18(1):51-8. doi: 10.1097/MOT.0b013e32835c5016.

Abstract

PURPOSE OF REVIEW

Mesenchymal stromal cells (MSCs) possess unique immunomodulatory features. MSCs dampen effector T-cell response while promoting the emergence of regulatory T cells. By skewing this balance, MSC could represent the ideal strategy for tolerance induction in organ transplantation. Here we review recent evidence on the efficacy of MSC-based therapy in experimental models of solid organ transplantation as well as the early clinical experiences in kidney transplantation.

RECENT FINDINGS

MSC infusion in experimental models of solid organ transplantation resulted in a Treg-mediated tolerance. MSC also synergized with low-dose or transient pharmacological immunosuppression in inducing long-term graft survival indicating that these cells could allow safe minimization of maintenance drug therapy. Early results from clinical studies in kidney transplant recipients reported encouraging results on the immunoregulatory effect of MSC, although posttransplant MSC infusion could associate with acute graft dysfunction (engraftment syndrome).

SUMMARY

Immunoregulatory functions of MSC are not fixed but rather the result of microenvironment they encounter in vivo. Further studies are needed to establish how and wherein these cells have to be administered and how they may function to safely modulate host immune response in vivo in clinical transplant setting.

摘要

目的综述

间充质基质细胞 (MSC) 具有独特的免疫调节功能。MSC 抑制效应 T 细胞反应,同时促进调节性 T 细胞的出现。通过这种平衡的倾斜,MSC 可能代表器官移植中诱导耐受的理想策略。本文综述了 MSC 治疗在实体器官移植实验模型中的最新证据,以及在肾移植中的早期临床经验。

最近的发现

MSC 输注在实体器官移植的实验模型中导致 Treg 介导的耐受。MSC 还与低剂量或短暂的药物免疫抑制协同作用,诱导长期移植物存活,表明这些细胞可以允许安全地减少维持药物治疗。在肾移植受者的临床研究早期结果报告了 MSC 的免疫调节作用令人鼓舞的结果,尽管移植后 MSC 输注可能与急性移植物功能障碍(植入综合征)相关。

总结

MSC 的免疫调节功能不是固定的,而是它们在体内遇到的微环境的结果。需要进一步的研究来确定如何以及在何处给予这些细胞,以及它们如何在体内的临床移植环境中安全地调节宿主免疫反应。

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