Therapeutic potential of mesenchymal stem cell‐derived extracellular vesicles in SARS‐CoV‐2 and H1N1 influenza‐induced acute lung injury

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Abstract
Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) have shown anti‐inflammatory potential in multiple inflammatory diseases. In the March 2022 issue of the Journal of Extracellular Vesicles, it was shown that EVs from human MSCs can suppress severe acute respiratory distress syndrome, coronavirus 2 (SARS‐CoV‐2) replication and can mitigate the production and release of infectious virions. We therefore hypothesized that MSC‐EVs have an anti‐viral effect in SARS‐CoV‐2 infection in vivo. We extended this question to ask whether also other respiratory viral infections could be treated by MSC‐EVs. Adipose stem cell‐derived EVs (ASC‐EVs) were isolated using tangential flow filtration from conditioned media obtained from a multi‐flask cell culture system. The effects of the ASC‐EVs were tested in Vero E6 cells in vitro. ASC‐EVs were also given i.v. to SARS‐CoV‐2 infected Syrian Hamsters, and H1N1 influenza virus infected mice. The ASC‐EVs attenuated SARS‐CoV‐2 virus replication in Vero E6 cells and reduced body weight and signs of lung injury in infected Syrian hamsters. Furthermore, ASC‐EVs increased the survival rate of influenza A‐infected mice and attenuated signs of lung injury. In summary, this study suggests that ASC‐EVs can have beneficial therapeutic effects in models of virus‐infection‐associated acute lung injury and may potentially be developed to treat lung injury in humans.

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