Acute respiratory distress syndrome (ARDS) induced by COVID-19 was a leading cause of severe illness and death during the pandemic, driven by an intense innate immune response, hyperinflammation, and a decrease in lymphocytes. Mesenchymal stromal cells (MSCs) represent a potential therapeutic option for ARDS due to their ability to modulate the immune system and inflammation. Our guests report results from a Health Canada–regulated Phase I and Phase II trials evaluating freshly cultured umbilical cord–derived MSCs in patients with COVID-19-related ARDS, including assessments of safety, maximum feasible tolerated dose, and preliminary efficacy. Their work explores a therapeutic strategy to improve ARDS outcomes using MSCs, which will be important for optimizing and targeting future cellular therapies.