Pooled evidence from preclinical and clinical studies for stem cell-based therapy in ARDS and COVID-19.

COVID-19 has severely devastated many lives across the globe. It has been speculated that stem cell-based therapy for COVID-19 treatment could be able to subsidize the effects. In preclinical and clinical studies, stem cell-based therapy has successfully eliminated inflammatory cytokines in ALI, ARDS, and COVID-19. Clinical trials have produced a variety of promising results for validating stem cell therapy in COVID-19 patients. For instance, exosome-based therapy (ExoFlow) showed an 87% survival status, and MSC-based therapy (Mesoblast) achieved an 83% survival rate in moderate to severe COVID-19 patients. This review debates the advantages of cell-free therapy, i.e., stem cell-derived exosome-based therapies, over stem cell-based therapy. This review aims to question whether the immunomodulatory effect of stem cells differs based on their origin and also tries to find possible answers for the best stem cells for treating SARS-CoV-2 infection. The role of stem cells and their extracellular vesicles in the upregulation of regulatory immune cells, growth factors (EGF, FGF, VEGF), and anti-inflammatory cytokines (IL-6, INF-α, galectin-1, notch-1, PDL-1) that promote the tissue regeneration at the injured site. The right side of the image depicts the downregulation of inflammation-inducing immune cells, pro-inflammatory cytokines, and chemokines that could also enhance COVID-19 therapy.