Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles in COVID-19-induced ARDS: Mechanisms of action, research progress, challenges, and opportunities

[Display omitted] •MSC therapy can attenuate cytokine storm and enhance alveolar fluid clearance.•MSC-derived EVs impede cytokine overproduction leading to immunity reconstitution.•Exosomes seem to be safer as they cannot form a tumor or lead to emboli formation.•Source of MSC, administration route, and optimal dose should be carefully evaluated.•Clinical-grade production and stability during MSC preparation are major challenges. In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city, Hubei province, China. Rapidly escalated into a worldwide pandemic, it has caused an unprecedented and devastating situation on the global public health and society economy. The severity of recent coronavirus disease, abbreviated to COVID-19, seems to be mostly associated with the patients’ immune response. In this vein, mesenchymal stromal/stem cells (MSCs) have been suggested as a worth-considering option against COVID-19 as their therapeutic properties are mainly displayed in immunomodulation and anti-inflammatory effects. Indeed, administration of MSCs can attenuate cytokine storm and enhance alveolar fluid clearance, endothelial recovery, and anti-fibrotic regeneration. Despite advantages attributed to MSCs application in lung injuries, there are still several issues __foremost probability of malignant transformation and incidence of MSCs-related coagulopathy__ which should be resolved for the successful application of MSC therapy in COVID-19. In the present study, we review the historical evidence of successful use of MSCs and MSC-derived extracellular vesicles (EVs) in the treatment of acute respiratory distress syndrome (ARDS). We also take a look at MSCs mechanisms of action in the treatment of viral infections, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if MSC therapy might be a promising therapeutic approach in COVID-19 patients.