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多能干细胞与器官移植中的免疫耐受诱导

Pluripotent stem cells and tolerance induction in organ transplantation.

作者信息

Imberti Barbara, Monti Manuela, Casiraghi Federica

机构信息

aCentro Anna Maria Astori, Parco Scientifico Tecnologico Kilometro Rosso, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo bCentro Ricerche di Medicina Rigenerativa-Fondazione IRCCS Policlinico San Matteo, Pavia cCentro Ricerche Trapianti 'Chiara Cucchi de Alessandri e Gilberto Crespi', IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy dFondazione IRCCS-Policlinico San Matteo, Pavia, Italy.

出版信息

Curr Opin Organ Transplant. 2015 Feb;20(1):86-93. doi: 10.1097/MOT.0000000000000144.

Abstract

PURPOSE OF REVIEW

Ongoing research is constantly looking for means to modulate the immune system for long-lasting engraftment of pluripotent stem cells (PSC) during stem cell-based therapies. This study reviews data on in-vitro and in-vivo immunogenicity of embryonic and induced-PSC and describes how their immunological properties can be harnessed for tolerance induction in organ transplantation.

RECENT FINDINGS

Although PSC display immunomodulatory properties in vitro, they are capable of eliciting an immune response that leads to cell rejection when transplanted into immune-competent recipients. Nevertheless, long-term acceptance of PSC-derived cells/tissues in an allogeneic environment can be achieved using minimal host conditioning. Protocols for differentiating PSC towards haematopoietic stem cells, thymic epithelial precursors, dendritic cells, regulatory T cells and myeloid-derived suppressor cells are being developed, suggesting the possibility to use PSC-derived immunomodulatory cells to induce tolerance to a solid organ transplant.

SUMMARY

PSC and/or their derivatives possess unique immunological properties that allow for acceptance of PSC-derived tissue with minimal host conditioning. Investigators involved either in regenerative or in transplant medicine must join their efforts with the ultimate aim of using PSC as a source of donor-specific cells that would create a protolerogenic environment to achieve tolerance in solid organ transplantation.

摘要

综述目的

正在进行的研究一直在寻找在基于干细胞的治疗过程中调节免疫系统以实现多能干细胞(PSC)长期植入的方法。本研究回顾了胚胎PSC和诱导PSC的体外和体内免疫原性数据,并描述了如何利用它们的免疫学特性在器官移植中诱导免疫耐受。

最新发现

尽管PSC在体外表现出免疫调节特性,但当移植到具有免疫能力的受体中时,它们能够引发免疫反应,导致细胞排斥。然而,使用最小程度的宿主预处理可以在同种异体环境中实现PSC衍生细胞/组织的长期接受。正在开发将PSC分化为造血干细胞、胸腺上皮前体细胞、树突状细胞、调节性T细胞和髓源性抑制细胞的方案,这表明有可能使用PSC衍生的免疫调节细胞来诱导对实体器官移植的耐受。

总结

PSC和/或其衍生物具有独特的免疫学特性,使得在最小程度的宿主预处理下能够接受PSC衍生的组织。参与再生医学或移植医学的研究人员必须共同努力,最终目标是将PSC用作供体特异性细胞的来源,从而创造一个促耐受环境,以实现实体器官移植中的耐受。

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