Opportunities and challenges of COVID-19 therapy using mesenchymal stem cells and their exosomes

ABSTRACT

BACKGROUND: Corona Virus Disease 2019 (COVID-19) is a highly contagious, rapidly variable, and dangerous infectious disease. However, no specific and effective treatment for COVID-19 is available until now. The safety and efficacy of mesenchymal stem cells and their exosomes have been well verified in numerous clinical trials. Their immunomodulatory and tissue regeneration capabilities may support them as a prospective therapy for COVID-19 application in the clinic. OBJECTIVE: To focus on the development, pathogenesis and the current treatment status of COVID-19, efficacy and possible immunomodulatory mechanisms of mesenchymal stem cells and their exosomes for COVID-19 so as to provide new insights into the clinical treatment for the disease in the future. METHODS: Articles were searched on PubMed and CNKI with the key words of "SARS-CoV-2, COVID-19, cytokine storm, acute respiratory distress syndrome, mesenchymal stem cells, exosomes, immune regulation, tissue repair” in Chinese and English. Finally, 64 articles were collected for this review. RESULTS AND CONCLUSION: Acute respiratory distress syndrome and acute lung injury caused by cytokine storm are the primary precipitating factors of death in individuals with COVID-19. Mesenchymal stem cells and their exosomes can effectively treat the symptoms of acute respiratory distress syndrome and repair the damaged lung tissue in COVID-19 patients by reducing the cytokine storm and promoting the regeneration of alveolar epithelial cells through the interaction with immune cells and their paracrine effects. All of these investigations confirmed that mesenchymal stem cells and their exosomes can fight the COVID-19 infection, and this might be a promising, safe and effective strategy. However, more preclinical studies and randomized, controlled clinical trials are needed to conduct the biodistribution, metabolic fate, and the potential treatment risks of mesenchymal stem cells and their derived exosomes in vivo to fully exploit their clinical efficacy. (English) [ABSTRACT FROM AUTHOR] 背景：2019 冠状病毒病 (Corona Virus Disease 2019，COVID-19) 的传播性强、变异速度快、且危害较大，目前没有针对 COVID-19 的特异治疗 策略。间充质干细胞及其外泌体的安全性和有效性已在众多临床试验中得到证实，其具有的免疫调节和组织修复能力，可作为COVID-19 前 瞻性疗法的主要应用依据，具有巨大的治疗潜力。 目的：重点阐述 COVID-19 的发生发展、致病机制、治疗现状，以及间充质干细胞与其衍生外泌体治疗 COVID-19 患者的有效性和可能的免疫 调控机制，为该疾病的临床治疗提供更多的理论参考。 方法：通过检索PubMed、中国知网数据库中收录的相关文献，英文搜索词为："SARS-CoV-2，COVID-19，cytokine storm，acute respiratory distress syndrome，mesenchymal stem cells，exosomes，immune regulation，tissue repair”，中文搜索词为："新型冠状病毒，2019 冠状病 毒病，细胞因子风暴，急性呼吸窘迫综合征，间充质干细胞，外泌体，免疫调节，组织修复”，最终对64篇文献进行归纳总结。 结果与结论：由细胞因子风暴所引起的急性呼吸窘迫综合征和急性肺损伤是导致 COVID-19 重症患者出现死亡的主要原因。间充质干细胞及 其外泌体通过与免疫细胞之间的相互作用及其旁分泌效应，降低 COVID-19 患者体内细胞因子风暴同时促进其肺泡上皮细胞再生，可有效治 疗急性呼吸窘迫综合征且能够修复其损伤肺组织，证明是一种能够对抗 COVID-19 感染且安全、有效的治疗策略。不过仍然需要更多的临床 前和随机对照临床试验对间充质干细胞及其外泌体移植后的生物分布、体内代谢命运、潜在风险进行更多的研究，以便于更充分发挥其临 床疗效。 (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo zu zhi gong cheng yan jiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)