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间充质干细胞及其作为细胞替代疗法和疾病建模工具的应用。

Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool.

作者信息

García-Castro J, Trigueros C, Madrenas J, Pérez-Simón J A, Rodriguez R, Menendez P

机构信息

Andalusian Stem Cell Bank (BACM), University of Granada, Granada, Spain.

出版信息

J Cell Mol Med. 2008 Dec;12(6B):2552-65. doi: 10.1111/j.1582-4934.2008.00516.x.

Abstract

Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas.

摘要

来自成体体细胞组织的间充质干细胞(MSCs)在体外和体内均可分化为多种中胚层组织,包括骨、软骨、脂肪组织、肌腱、韧带甚至肌肉。MSCs优先归巢至受损组织并在其中发挥其治疗潜力。MSCs的一个显著特征是其固有的低免疫原性,因为它们几乎不会诱导同种异体淋巴细胞和抗原呈递细胞增殖(即便有增殖,也是极少的)。相反,MSCs在体外似乎具有免疫抑制作用。它们的多谱系分化潜能及其免疫特惠特性正在全球范围内被用于自体和异体细胞替代策略。在此,我们向读者介绍MSCs的生物学特性以及免疫耐受的潜在机制。然后,我们概述基于MSCs免疫特性的潜在细胞替代策略和临床应用。讨论了正在进行的移植物抗宿主病、与造血干细胞共移植后MSCs促进造血恢复以及组织修复的临床试验。最后,我们综述了基于将MSCs用作自发或诱导性肿瘤转化的靶细胞亚群以及用于模拟非血液系统间充质癌(如肉瘤)的新兴领域。

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