Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cel...

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Autores principales: Caryn Cloer, Laila Roudsari, Lauren Rochelle, Timothy Petrie, Michaela Welch, Joseph Charest, Kelly Tan, Li Fugang, Thomas Petersen, Roger Ilagan, Sarah Hogan
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/c96ccb35f14f4e1db9e634676aa3eb8d
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spelling oai:doaj.org-article:c96ccb35f14f4e1db9e634676aa3eb8d2021-11-25T06:10:53ZMesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-191932-6203https://doaj.org/article/c96ccb35f14f4e1db9e634676aa3eb8d2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592477/?tool=EBIhttps://doaj.org/toc/1932-6203Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.Caryn CloerLaila RoudsariLauren RochelleTimothy PetrieMichaela WelchJoseph CharestKelly TanLi FugangThomas PetersenRoger IlaganSarah HoganPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Caryn Cloer
Laila Roudsari
Lauren Rochelle
Timothy Petrie
Michaela Welch
Joseph Charest
Kelly Tan
Li Fugang
Thomas Petersen
Roger Ilagan
Sarah Hogan
Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19
description Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.
format article
author Caryn Cloer
Laila Roudsari
Lauren Rochelle
Timothy Petrie
Michaela Welch
Joseph Charest
Kelly Tan
Li Fugang
Thomas Petersen
Roger Ilagan
Sarah Hogan
author_facet Caryn Cloer
Laila Roudsari
Lauren Rochelle
Timothy Petrie
Michaela Welch
Joseph Charest
Kelly Tan
Li Fugang
Thomas Petersen
Roger Ilagan
Sarah Hogan
author_sort Caryn Cloer
title Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19
title_short Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19
title_full Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19
title_fullStr Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19
title_full_unstemmed Mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: Implications for COVID-19
title_sort mesenchymal stromal cell-derived extracellular vesicles reduce lung inflammation and damage in nonclinical acute lung injury: implications for covid-19
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/c96ccb35f14f4e1db9e634676aa3eb8d
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