Potential Application of Mesenchymal Stem Cells and Their Exosomes in Lung Injury: An Emerging Therapeutic Option for COVID-19 Patients

The authors shed light on the mechanistic view of MSC therapeutic role based on preclinical and clinical studies on acute lung injury and ARDS; therefore, offering a unique correlation and applicability in COVID-19 patients. They further highlight the challenges and opportunities in the use of MSC-based therapy.
[Stem Cell Research & Therapy]
Al-Khawaga, S., & Abdelalim, E. M. (2020). Potential application of mesenchymal stem cells and their exosomes in lung injury: an emerging therapeutic option for COVID-19 patients. Stem Cell Research & Therapy, 11(1), 437. https://doi.org/10.1186/s13287-020-01963-6 Cite
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First Patient Dosed in Phase II Trial to Treat Complications in COVID-19

Arch Biopartners, Inc. announced it has dosed the first patient in the Phase II trial of its lead drug LSALT peptide, targeting prevention of acute lung injury, acute kidney injury and other complications caused by inflammation in hospitalized patients with moderate to severe cases of COVID-19.
[Arch Biopartners, Inc.]
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Mesenchymal Stem Cells Reverse EMT Process through Blocking the Activation of NF-κB and Hedgehog Pathways in LPS-Induced Acute Lung Injury

Researchers investigated the mechanism underneath MSC-reversed lung injury and fibrosis. They determined that coculture with MSC led to the inactivation of NF-κB signaling and therefore suppressed the hedgehog pathway in LPS-treated MLE-12 cells.
[Cell Death & Disease]
Xiao, K., He, W., Guan, W., Hou, F., Yan, P., Xu, J., Zhou, T., Liu, Y., & Xie, L. (2020). Mesenchymal stem cells reverse EMT process through blocking the activation of NF-κB and Hedgehog pathways in LPS-induced acute lung injury. Cell Death & Disease, 11(10), 1–17. https://doi.org/10.1038/s41419-020-03034-3 Cite
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An Aberrant STAT Pathway Is Central to COVID-19

Scientists discuss the possibility of using various approved drugs, or drugs currently in clinical development, to treat COVID-19. They suggest to enhance STAT1 activity and/or inhibit STAT3 functions for COVID-19 treatment.
[Cell Death & Differentiation]
Matsuyama, T., Kubli, S. P., Yoshinaga, S. K., Pfeffer, K., & Mak, T. W. (2020). An aberrant STAT pathway is central to COVID-19. Cell Death & Differentiation, 1–17. https://doi.org/10.1038/s41418-020-00633-7 Cite
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Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury by Inhibiting the Proinflammatory Function of Ly6C+ CD8+ T Cells

Investigators showed that CD8+ T cells played an important role in MSC-mediated acute lung injury remission, and both infiltration quantity and proinflammatory function were inhibited by MSCs, indicating a potential mechanism for therapeutic intervention.
[Cell Death & Disease]
Zhu, J., Feng, B., Xu, Y., Chen, W., Sheng, X., Feng, X., Shi, X., Liu, J., Pan, Q., Yu, J., Li, L., & Cao, H. (2020). Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C + CD8 + T cells. Cell Death & Disease, 11(10), 1–11. https://doi.org/10.1038/s41419-020-03036-1 Cite
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STAT3–BDNF–TrkB Signaling Promotes Alveolar Epithelial Regeneration after Lung Injury

Single-cell transcriptome analysis identified brain-derived neurotrophic factor as a STAT3 target gene with newly accessible chromatin in a unique population of regenerating AT2 cells.
[Nature Cell Biology]
Paris, A. J., Hayer, K. E., Oved, J. H., Avgousti, D. C., Toulmin, S. A., Zepp, J. A., Zacharias, W. J., Katzen, J. B., Basil, M. C., Kremp, M. M., Slamowitz, A. R., Jayachandran, S., Sivakumar, A., Dai, N., Wang, P., Frank, D. B., Eisenlohr, L. C., Cantu, E., Beers, M. F., … Worthen, G. S. (2020). STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-020-0569-x Cite
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Aging Impairs Alveolar Epithelial Type II Cell Function in Acute Lung Injury

Alveolar epithelial type II cells (AE2) of young mice adapted to injury by increasing intracellular surfactant volume and proliferation rate. In old mice, however, this adaptive response was compromised and AE2 of old mice showed signs of cell senescence, increased inflammatory signaling and impaired surfactant metabolism in acute lung injury.
[American Journal of Physiology-Lung Cellular and Molecular Physiology]
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Ruscogenin Attenuates Particulate Matter-Induced Acute Lung Injury in Mice via Protecting Pulmonary Endothelial Barrier and Inhibiting TLR4 Signaling Pathway

The authors investigated whether and how ruscogenin (RUS) exerted therapeutic effects on PM-induced acute lung injury. RUS was orally administered to mice prior to or after intratracheal instillation of particulate matter suspension.
[Acta Pharmacologica Sinica]
Wang, Y., Wu, Y., Zhang, J., Tang, J., Fan, R., Li, F., Yu, B., Kou, J., & Zhang, Y. (2020). Ruscogenin attenuates particulate matter-induced acute lung injury in mice via protecting pulmonary endothelial barrier and inhibiting TLR4 signaling pathway. Acta Pharmacologica Sinica, 1–9. https://doi.org/10.1038/s41401-020-00502-6 Cite
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Lung-Derived HMGB1 Is Detrimental for Vascular Remodeling of Metabolically Imbalanced Arterial Macrophages

Acute lung injury-induced HMGB1 leaked and was captured by arterial macrophages thereby altering their mitochondrial metabolism through RIPK3.
[Nature Communications]
Boytard, L., Hadi, T., Silvestro, M., Qu, H., Kumpfbeck, A., Sleiman, R., Fils, K. H., Alebrahim, D., Boccalatte, F., Kugler, M., Corsica, A., Gelb, B. E., Jacobowitz, G., Miller, G., Bellini, C., Oakes, J., Silvestre, J.-S., Zangi, L., & Ramkhelawon, B. (2020). Lung-derived HMGB1 is detrimental for vascular remodeling of metabolically imbalanced arterial macrophages. Nature Communications, 11(1), 4311. https://doi.org/10.1038/s41467-020-18088-2 Cite
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Vasomune Receives a US $2.8 Million PRMRP Grant from the US Department of Defense to Develop AV-001 for the Treatment of ALI/ARDS of Any Cause, Including COVID-19

Vasomune Therapeutics announced it has received a Peer-Reviewed Medical Research Program grant award effective August 1, 2020 for US $2.8 million from the US Department of Defense for the development AV-001 for the treatment of COVID-19-associated acute lung injury and acute respiratory distress syndrome.
[Vasomune Therapeutics]
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MicroRNA-377-3p Released by Mesenchymal Stem Cell Exosomes Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Targeting RPTOR to Induce Autophagy

Investigators found lipopolysaccharide significantly increased inflammatory factors, administration of exosomes released by human umbilical cord MSCs successfully improved lung morphometry.
[Cell Death & Disease]
Wei, X., Yi, X., Lv, H., Sui, X., Lu, P., Li, L., An, Y., Yang, Y., Yi, H., & Chen, G. (2020). MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy. Cell Death & Disease, 11(8), 1–14. https://doi.org/10.1038/s41419-020-02857-4 Cite
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