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

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–cel...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-09, Vol.10 (9), p.2393
Main Authors: Park, Jae Hyun, Choi, Yuri, Lim, Chul-Woo, Park, Ji-Min, Yu, Shin-Hye, Kim, Yujin, Han, Hae Jung, Kim, Chun-Hyung, Song, Young-Sook, Kim, Chul, Yu, Seung Rok, Oh, Eun Young, Lee, Sang-Myeong, Moon, Jisook
Format: Article
Language:English
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Antiviral agents
Cell differentiation
Cell interactions
Coronaviruses
COVID-19
cytokine storm
extracellular vesicle
Extracellular vesicles
Genomes
Immune response
Inflammation
mesenchymal stem cell
Mesenchymal stem cells
Microenvironments
MicroRNAs
miRNA
Mutation
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Stem cells
Viral infections
Viruses
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10092393