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

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.

The role of microRNAs in solving COVID-19 puzzle from infection to therapeutics: A mini-review

“…Since researchers predicted that the vast majority of the target genes of the detected miRNAs are related to the assembly of the viral replication machinery, and inflammatory responses, the antiviral properties of MSC-EVs were attributed to the regulatory roles of these tiny RNA molecules. In summary, these findings support the fact that MSC-EVs could represent a promising alternative to treat multiple variants of SARS-CoV-2 ( Park et al, 2021 ).…”

Integrated miRNA/cytokine/chemokine profiling reveals severity-associated step changes and principal correlates of fatality in COVID-19

“…It has been proposed that miRNAs might be involved in controlling inflammation during COVID-19 (Aslani et al, 2021;Gasparello et al, 2021;Houshmandfar et al, 2021;Matarese et al, 2020;Plowman and Lagos, 2021). Theoretical CC/miRNA regulatory networks have been proposed but not validated (Khokhar et al, 2022), whereas the potential of miRNA-like therapeutics has also been suggested (Ahn et al, 2021;Dash et al, 2021;Hum et al, 2021;Park et al, 2021). Of note, initial studies have identified potential changes in miRNA expression in COVID-19 and signatures from targeted testing of 41 miRNAs have been linked to ICU treatment and mortality in a Spanish cohort (de Gonzalo-Calvo et al, 2021).…”

Noncoding RNA in Extracellular Vesicles Regulate Differentiation of Mesenchymal Stem Cells

“…miR-1470 is one of the exosomal biomarkers of BMSCs for its high expression when exosomes from fibroblast serve as the control (71). Equipped with miR-92a-3p, miR-26a-5p, miR-23a-3p, miR-103a-3p, and miR-181a-5p, exosome from neuronal stem cell has therapeutic potential (78).…”