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间充质干细胞作为胰岛移植的饲养层细胞

Mesenchymal stem cells as feeder cells for pancreatic islet transplants.

作者信息

Sordi Valeria, Piemonti Lorenzo

机构信息

San Raffaele Diabetes Research Institute (HSR-DRI), Division of Immunology, Transplantation and Infectious Disease, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.

出版信息

Rev Diabet Stud. 2010 Summer;7(2):132-43. doi: 10.1900/RDS.2010.7.132. Epub 2010 Aug 10.

Abstract

Allogeneic islet transplantation serves as a source of insulin-secreting beta-cells for the maintenance of normal glucose levels and treatment of diabetes. However, limited availability of islets, high rates of islet graft failure, and the need for life-long non-specific immunosuppressive therapy are major obstacles to the widespread application of this therapeutic approach. To overcome these problems, pancreatic islet transplantation was recently suggested as a potential target of the "therapeutic plasticity" of adult stem cells. In fact, new results suggest that stem/precursor cells, and mesenchymal stem cells in particular, co-transplanted with islets can promote tissue engraftment and beta-cell survival via bystander mechanisms, mainly exerted by creating a milieu of cytoprotective and immunomodulatory molecules. This evidence consistently challenges the limited view that stem/precursor cells work exclusively through beta-cell replacement in diabetes therapy. It proposes that stem cells also act as "feeder" cells for islets, and supporter of graft protection, tissue revascularization, and immune acceptance. This article reviews the experience of using stem cell co-transplantation as strategy to improve islet transplantation. It highlights that comprehension of the mechanisms involved will help to identify new molecular targets and promote development of new pharmacological strategies to treat type 1 and type 2 diabetes patients.

摘要

同种异体胰岛移植可作为分泌胰岛素的β细胞来源,用于维持正常血糖水平和治疗糖尿病。然而,胰岛供应有限、胰岛移植失败率高以及需要终身进行非特异性免疫抑制治疗是这种治疗方法广泛应用的主要障碍。为克服这些问题,胰腺胰岛移植最近被认为是成体干细胞“治疗可塑性”的一个潜在靶点。事实上,新的研究结果表明,干细胞/前体细胞,尤其是间充质干细胞,与胰岛共同移植可通过旁观者机制促进组织植入和β细胞存活,主要是通过产生细胞保护和免疫调节分子的微环境来实现。这一证据不断挑战干细胞/前体细胞在糖尿病治疗中仅通过β细胞替代发挥作用的有限观点。它提出干细胞还可作为胰岛的“饲养”细胞,以及移植保护、组织血管再生和免疫耐受的支持者。本文综述了将干细胞共同移植作为改善胰岛移植策略的经验。它强调,理解其中涉及的机制将有助于确定新的分子靶点,并促进开发治疗1型和2型糖尿病患者的新药理学策略。

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Mesenchymal stem cells as feeder cells for pancreatic islet transplants.间充质干细胞作为胰岛移植的饲养层细胞
Rev Diabet Stud. 2010 Summer;7(2):132-43. doi: 10.1900/RDS.2010.7.132. Epub 2010 Aug 10.

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