Lung Microphysiological System Validates Novel Cell Therapy for Acute Respiratory Distress Syndrome

Abstract Acute Respiratory Distress Syndrome (ARDS) is a life‐threatening condition characterized by severe inflammation and lung damage, leading to critical hypoxemia. Despite its high mortality rate, the only currently available treatment, Dexamethasone, is associated with significant side effects. This study aims to evaluate the efficacy of primed human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐pMSCs) as a potential alternative treatment for ARDS. A novel lung microphysiological system (MPS) modeling the lung environment is developed and treated with lipopolysaccharide (LPS) to simulate ARDS. The effects of hUCB‐pMSCs and dexamethasone are compared using state‐of‐the‐art methods, including fluorescence‐based imaging and single‐cell RNA sequencing. The hUCB‐pMSCs significantly activated angiogenesis‐related pathways in endothelial cells and enhanced the formation of tip‐like endothelial cells involved in new blood vessel formation. These findings are corroborated by fluorescence microscopy, demonstrating the robust potential of hUCB‐pMSCs as a therapeutic approach. Overall, the results support the potential of hUCB‐pMSCs as a promising alternative treatment for ARDS.