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Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2.
Cells. 2021 09 12; 10(9)C

Abstract

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34572043

Citation

Park, Jae Hyun, et al. "Potential Therapeutic Effect of Micrornas in Extracellular Vesicles From Mesenchymal Stem Cells Against SARS-CoV-2." Cells, vol. 10, no. 9, 2021.
Park JH, Choi Y, Lim CW, et al. Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2. Cells. 2021;10(9).
Park, J. H., Choi, Y., Lim, C. W., Park, J. M., Yu, S. H., Kim, Y., Han, H. J., Kim, C. H., Song, Y. S., Kim, C., Yu, S. R., Oh, E. Y., Lee, S. M., & Moon, J. (2021). Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2. Cells, 10(9). https://doi.org/10.3390/cells10092393
Park JH, et al. Potential Therapeutic Effect of Micrornas in Extracellular Vesicles From Mesenchymal Stem Cells Against SARS-CoV-2. Cells. 2021 09 12;10(9) PubMed PMID: 34572043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential Therapeutic Effect of Micrornas in Extracellular Vesicles from Mesenchymal Stem Cells against SARS-CoV-2. AU - Park,Jae Hyun, AU - Choi,Yuri, AU - Lim,Chul-Woo, AU - Park,Ji-Min, AU - Yu,Shin-Hye, AU - Kim,Yujin, AU - Han,Hae Jung, AU - Kim,Chun-Hyung, AU - Song,Young-Sook, AU - Kim,Chul, AU - Yu,Seung Rok, AU - Oh,Eun Young, AU - Lee,Sang-Myeong, AU - Moon,Jisook, Y1 - 2021/09/12/ PY - 2021/08/09/received PY - 2021/08/31/revised PY - 2021/09/09/accepted PY - 2021/9/28/entrez PY - 2021/9/29/pubmed PY - 2021/10/8/medline KW - COVID-19 KW - SARS-CoV-2 KW - cytokine storm KW - extracellular vesicle KW - mesenchymal stem cell KW - miRNA JF - Cells JO - Cells VL - 10 IS - 9 N2 - 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. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/34572043/Potential_Therapeutic_Effect_of_Micrornas_in_Extracellular_Vesicles_from_Mesenchymal_Stem_Cells_against_SARS_CoV_2_ L2 - https://www.mdpi.com/resolver?pii=cells10092393 DB - PRIME DP - Unbound Medicine ER -