Mechanisms of Potential Therapeutic Utilization of Mesenchymal Stem Cells in COVID-19 Treatment.

The 2019 novel coronavirus disease (COVID-19) has lasted for over 3 years and has seriously affected the regular life trajectory of human beings. The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has caused non-negligible harm to people's respiratory systems and multiple organs. Although the pathogenesis of COVID-19 has been fully elucidated, there is still a lack of effective and specific treatment for COVID-19. Mesenchymal stem cells (MSCs) or MSC-derived extracellular vesicles (MSC-EVs) by far have become the most promising candidates in preclinical studies and clinical trials, and MSC-related therapies have shown their potential to treat severe COVID-19. The multidirectional differentiation potential and immunomodulatory function of MSCs have allowed the cells to exert multiple cellular and molecular actions on different immune cells and organs. It is critical to understand the therapeutic roles of MSCs before entering the clinics for COVID-19 and other diseases. This review summarizes the recent progress of particular mechanisms underlying the immunomodulatory and tissue regenerative effects of MSCs toward COVID-19. We focused on discussing the functional roles of MSC-mediated effects on immune cell responses, cell survival, and organ regeneration. Besides, the novel discoveries and recent findings of MSC clinical application in patients with COVID-19 were highlighted. This will provide an overview of the current research on the rapid development of MSC-based therapies not only for COVID-19 but also for other immune-mediated/immune-dysregulating diseases.