Tsuchiya Atsunori, Takeuchi Suguru, Iwasawa Takahiro, Kumagai Masaru, Sato Takeki, Motegi Satoko, Ishii Yui, Koseki Youhei, Tomiyoshi Kei, Natsui Kazuki, Takeda Nobutaka, Yoshida Yuki, Yamazaki Fusako, Kojima Yuichi, Watanabe Yusuke, Kimura Naruhiro, Tominaga Kentaro, Kamimura Hiroteru, Takamura Masaaki, Terai Shuji
Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510 Japan.
Inflamm Regen. 2020 Jun 22;40:14. doi: 10.1186/s41232-020-00121-y. eCollection 2020.
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.
新型冠状病毒严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是2019冠状病毒病（COVID-19）及随后全球大流行的病原体。该病毒的传播产生了全球性影响，如活动限制、经济停滞和医疗基础设施崩溃。严重的SARS-CoV-2感染会引发细胞因子风暴，导致急性呼吸窘迫综合征（ARDS）和多器官功能衰竭，这些都是非常严重的健康状况，必须尽快缓解或解决。间充质干细胞（MSCs）及其外泌体可通过诱导抗炎巨噬细胞、调节性T细胞和B细胞以及调节性树突状细胞来影响免疫细胞，并可使T细胞失活。因此，它们是治疗重症COVID-19的潜在候选药物。在本综述中，我们报告了重症COVID-19的背景、MSCs及其外泌体的基本方面和作用机制，并讨论了基于MSCs和外泌体治疗流感诱导的ARDS的基础和临床研究。最后，我们报告了在ClinicalTrials.gov上13个国家注册的最近启动或计划进行的MSCs（33项试验）和外泌体（1项试验）治疗重症COVID-19的临床试验中，MSCs和外泌体疗法的潜力。
