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干细胞衍生的外泌体和 microRNAs 在脊髓损伤中的作用。

Role of Stem Cell-Derived Exosomes and microRNAs in Spinal Cord Injury.

机构信息

Department of Physiology, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.

Department of Neurosurgery, Kangwon National University School of Medicine, Chuncheon 24341, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Sep 8;24(18):13849. doi: 10.3390/ijms241813849.

Abstract

Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side effects, such as inducing orthostatic arterial hypotension due to the blockade of alpha receptors, cardiotoxic effects due to impaired repolarization, and atrioventricular block and tachycardia, including ventricular fibrillation. These challenges have driven the medical community to seek effective treatments for this serious global health threat. Mesenchymal stem cells (MSCs) are pluripotent cells with anti-inflammatory, anti-apoptotic, and immunomodulatory properties, providing a promising alternative due to their ability to differentiate, favorable culture conditions, in vitro manipulation ability, and robust properties. Although MSCs themselves rarely differentiate into neurons at the site of injury after transplantation in vivo, paracrine factors secreted by MSCs can create environmental conditions for cell-to-cell communication and have shown therapeutic effects. Recent studies have shown that the pleiotropic effects of MSCs, particularly their immunomodulatory potential, can be attributed primarily to these paracrine factors. Exosomes derived from MSCs are known to play an important role in these effects. Many studies have evaluated the potential of exosome-based therapies for the treatment of various neurological diseases. In addition to exosomes, various miRNAs derived from MSCs have been identified to regulate genes and alleviate neuropathological changes in neurodegenerative diseases. This review explores the burgeoning field of exosome-based therapies, focusing on the effects of MSC-derived exosomes and exosomal miRNAs, and summarizes recent findings that shed light on the potential of exosomes in the treatment of neurological disorders. The insights gained from this review may pave the way for innovative and effective treatments for these complex conditions. Furthermore, we suggest the therapeutic effects of exosomes and exosomal miRNAs from MSCs, which have a rescue potential in spinal cord injury via diverse signaling pathways.

摘要

神经系统疾病是全球性的健康问题。目前的药物治疗方法通常只能在短期内缓解症状,但会产生剂量依赖性的副作用,如因阻断α受体而导致直立性动脉低血压、因复极化受损而导致的心脏毒性作用、房室传导阻滞和心动过速,包括室颤。这些挑战促使医学界寻求有效治疗这种严重的全球健康威胁的方法。间充质干细胞(MSCs)是具有抗炎、抗凋亡和免疫调节特性的多能细胞,由于其分化能力、良好的培养条件、体外操作能力和强大的特性,为这一严重的全球健康威胁提供了有希望的替代方法。虽然 MSCs 本身在体内移植后很少在损伤部位分化为神经元,但 MSCs 分泌的旁分泌因子可以为细胞间通讯创造环境条件,并显示出治疗效果。最近的研究表明,MSCs 的多效性效应,特别是其免疫调节潜能,可以主要归因于这些旁分泌因子。MSCs 衍生的外泌体在这些效应中起着重要作用。许多研究评估了基于外泌体的治疗方法治疗各种神经疾病的潜力。除了外泌体,还鉴定了来自 MSCs 的各种 miRNA 来调节基因并减轻神经退行性疾病中的神经病理变化。本综述探讨了基于外泌体的治疗方法的新兴领域,重点关注 MSC 衍生的外泌体和外泌体 miRNA 的作用,并总结了最近的发现,这些发现揭示了外泌体在治疗神经疾病中的潜力。从这项综述中获得的见解可能为这些复杂疾病的创新和有效治疗铺平道路。此外,我们提出了 MSC 来源的外泌体和外泌体 miRNA 的治疗作用,它们通过多种信号通路具有脊髓损伤的抢救潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2187/10530823/8b1c9298e746/ijms-24-13849-g001.jpg

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