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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\u2010derived mesenchymal stem cells (hUCB\u2010pMSCs) 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\u2010pMSCs and dexamethasone are compared using state\u2010of\u2010the\u2010art methods, including fluorescence\u2010based imaging and single\u2010cell RNA sequencing. The hUCB\u2010pMSCs significantly activated angiogenesis\u2010related pathways in endothelial cells and enhanced the formation of tip\u2010like endothelial cells involved in new blood vessel formation. These findings are corroborated by fluorescence microscopy, demonstrating the robust potential of hUCB\u2010pMSCs as a therapeutic approach. 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