Harnessing CD146-positive mesenchymal stromal cells for precision therapy in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that is characterized by high mortality rates and limited therapeutic options. Notably, Zhang <i>et al</i> demonstrated that CD146+ mesenchymal stromal cells (MSCs) exhibited greater therapeutic efficacy than CD146- MSCs. These cells enhance epithelial repair through nuclear factor kappa B/cyclooxygenase-2-associated paracrine signaling and secretion of pro-angiogenic factors. We concur that MSCs hold significant promise for ARDS treatment; however, the heterogeneity of cell products is a translational barrier. Phenotype-aware strategies, such as CD146 enrichment, standardized potency assays, and extracellular vesicle profiling, are essential for improving the consistency of these studies. Furthermore, advanced preclinical models, such as lung-on-a-chip systems, may provide more predictive insights into the therapeutic mechanisms. This article underscores the importance of CD146+ MSCs in ARDS, emphasizes the need for precision in defining cell products, and discusses how integrating subset selection into translational pipelines could enhance the clinical impact of MSC-based therapies.