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简明综述:神经退行性疾病中的间充质干细胞

Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases.

作者信息

Volkman Rotem, Offen Daniel

机构信息

Tel Aviv University, Tel Aviv-Yafo, Israel.

出版信息

Stem Cells. 2017 Aug;35(8):1867-1880. doi: 10.1002/stem.2651. Epub 2017 Jun 30.

Abstract

Stem cell-based therapies for neurodegenerative diseases aim at halting clinical deterioration by regeneration and by providing local support for damaged tissue. Mesenchymal stem cells (MSCs) hold great potential for cell therapy as they can be efficiently derived from adult tissue, ex vivo expanded in culture and safely transplanted autologously. MSCs were also shown to be able to differentiate toward neural fates and to secrete a broad range of factors able to promote nervous tissue maintenance and repair. Moreover, upon transplantation, MSCs were shown capable of homing toward lesioned areas, implying their potential use as vehicles for therapeutic agents administration. Indeed, various advantageous effects were reported following human MSCs transplantation into rodent models of neurodegenerative diseases, such as neurotrophic factor-mediated protection, enhanced neurogenesis, modulation of inflammation, and abnormal protein aggregate clearance. Per journal style, most nonstandard abbreviations must be used at least two times in the abstract to be retained; NTF was used once and thus has been deleted. Recent studies have also used ex vivo manipulation for enhanced expression of potentially favorable factors, by so exploiting the homing capacity of MSCs for effective expression at the lesion site. Here, we will summarize current advancements in MSCs-based therapies for neurodegenerative diseases. We will examine the roles of central mechanisms suggested to mediate the beneficial effects of MSCs-based therapy and consider the augmentation of these mechanisms for superior clinical outcomes in rodent models of neurodegeneration as well as in clinical trials. Stem Cells 2017;35:1867-1880.

摘要

基于干细胞的神经退行性疾病治疗旨在通过再生以及为受损组织提供局部支持来阻止临床病情恶化。间充质干细胞(MSCs)在细胞治疗方面具有巨大潜力,因为它们可以从成人组织中高效获取,在体外培养中扩增,并能安全地进行自体移植。研究还表明,MSCs能够向神经命运分化,并分泌多种能够促进神经组织维持和修复的因子。此外,移植后,MSCs能够归巢至损伤区域,这意味着它们有可能用作治疗药物的递送载体。实际上,将人MSCs移植到神经退行性疾病的啮齿动物模型后,已报道了各种有益效果,如神经营养因子介导的保护作用、增强神经发生、调节炎症以及清除异常蛋白质聚集体。按照期刊风格,大多数非标准缩写在摘要中必须至少使用两次才能保留;NTF仅使用了一次,因此已被删除。最近的研究还通过利用MSCs的归巢能力在损伤部位有效表达潜在有利因子,对其进行体外操作以增强这些因子的表达。在此,我们将总结基于MSCs的神经退行性疾病治疗的当前进展。我们将研究被认为介导基于MSCs治疗有益效果的核心机制的作用,并考虑增强这些机制以在神经退行性疾病的啮齿动物模型以及临床试验中获得更好的临床结果。《干细胞》2017年;35卷:1867 - 1880页

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