Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies.

中文翻译：

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COVID-19 中基于间充质干细胞的治疗和外泌体：当前趋势和前景

2019 年新型冠状病毒病 (COVID-19) 是由严重急性呼吸综合征冠状病毒 2 型引起的。该病毒会引起过度的免疫反应，导致细胞因子风暴和急性呼吸窘迫综合征，这是导致 COVID-19 相关死亡率和发病率的主要原因。到目前为止，没有任何疗法能够成功规避与 COVID-19 相关的加剧的免疫反应或细胞因子风暴。间充质干细胞 (MSCs) 通过其免疫调节和再生活性，主要由其旁分泌作用和细胞外囊泡产生介导，在许多自身免疫、炎症和退行性疾病中具有治疗潜力。在本文中，我们回顾了使用 MSCs 治疗 COVID-19 的临床研究，包括 MSCs 对 COVID-19 的病理生理学和细胞因子风暴的免疫调节的有益作用。总结了正在进行的临床试验设计、细胞来源、剂量和给药方式以及人群，并讨论了旁分泌的获益模式。我们还为优化基于 MSC 的疗法提供建议，包括基因工程、细胞表面修饰策略、纳米技术应用和联合疗法。