Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2

Cells

Sang-Myeong Lee¹  Yuri Choi²  Jisook Moon²  Chul-Woo Lim²  Ji-Min Park²  Jae Hyun Park²  Chul Kim²  Young-Sook Song²  Eun Young Oh³  Seung Rok Yu³  Shin-Hye Yu⁴  Chun-Hyung Kim⁴  Yujin Kim⁴  Hae Jung Han⁵ 

[1] College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea;Department of Biotechnology, College of Life Science, CHA University, Seongnam 13488, Korea;Division of Biotechnology, College of Environmental and Bioresources, Jeonbuk National University, Iksan 54596, Korea;Paean Biotechnology, Incorporation, Daejeon 34028, Korea;Research and Development Center, Green Cross WellBeing Corporation, Seongnam 13595, Korea;

关键词: SARS-CoV-2;    COVID-19;    miRNA;    mesenchymal stem cell;    extracellular vesicle;    cytokine storm;   

DOI  :  10.3390/cells10092393

来源: DOAJ

【 摘 要 】

Extracellular vesicles (EVs) are cell-released, nanometer-scaled, membrane-bound materials and contain diverse contents including proteins, small peptides, and nucleic acids. Once released, EVs can alter the microenvironment and regulate a myriad of cellular physiology components, including cell–cell communication, proliferation, differentiation, and immune responses against viral infection. Among the cargoes in the vesicles, small non-coding micro-RNAs (miRNAs) have received attention in that they can regulate the expression of a variety of human genes as well as external viral genes via binding to the complementary mRNAs. In this study, we tested the potential of EVs as therapeutic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. First, we found that the mesenchymal stem-cell-derived EVs (MSC-EVs) enabled the rescue of the cytopathic effect of SARS-CoV-2 virus and the suppression of proinflammatory responses in the infected cells by inhibiting the viral replication. We found that these anti-viral responses were mediated by 17 miRNAs matching the rarely mutated, conserved 3′-untranslated regions (UTR) of the viral genome. The top five miRNAs highly expressed in the MSC-EVs, miR-92a-3p, miR-26a-5p, miR-23a-3p, miR-103a-3p, and miR-181a-5p, were tested. They were bound to the complemented sequence which led to the recovery of the cytopathic effects. These findings suggest that the MSC-EVs are a potential candidate for multiple variants of anti-SARS-CoV-2.

【 授权许可】

Unknown