ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.
ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles.
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DOI：
10.3389/fncel.2017.00080
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发表时间：
2017
影响因子：
5.3
通讯作者：
Mariotti R
中科院分区：
文献类型：
--
作者：
Bonafede R;Mariotti R
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种以运动皮层、脑干和脊髓运动神经元变性为特征的进行性肌肉瘫痪的神经退行性疾病。ALS的发病机制尚不清楚，尽管大量的研究表明，一些改变的信号通路，如线粒体功能障碍，谷氨酸兴奋性毒性，氧化应激和神经炎症的参与。迄今为止，所提出的治疗策略针对这些改变中的一个或几个，对ALS患者的病程和生存率的影响很小。ALS发病机制中不同机制的参与强调了针对多个方面的治疗方法的需要。间充质干细胞（MSC）可以支持运动神经元和周围细胞，减轻炎症，刺激组织再生和释放生长因子。在此基础上，MSC已被提出作为治疗ALS的有希望的候选者。然而，由于细胞治疗的缺点，由干细胞释放的细胞外囊泡（EV）的可能的治疗用途引起了越来越多的兴趣。本文综述了ALS的主要病理机制和目前提出的相关治疗方法，重点介绍了MSC治疗及其临床前和临床应用。此外，EV的性质和特点及其在再现干细胞的作用进行了讨论，阐明如何以及为什么这些囊泡可以提供新的机会ALS治疗。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients. The involvement of different mechanisms in ALS pathogenesis underlines the need for a therapeutic approach targeted to multiple aspects. Mesenchymal stem cells (MSC) can support motoneurons and surrounding cells, reduce inflammation, stimulate tissue regeneration and release growth factors. On this basis, MSC have been proposed as promising candidates to treat ALS. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles (EVs) released by stem cells is raising increasing interest. The present review summarizes the main pathological mechanisms involved in ALS and the related therapeutic approaches proposed to date, focusing on MSC therapy and their preclinical and clinical applications. Moreover, the nature and characteristics of EVs and their role in recapitulating the effect of stem cells are discussed, elucidating how and why these vesicles could provide novel opportunities for ALS treatment.