Beyond immunomodulation: mechanisms and synergistic strategies of mesenchymal stem cells in promoting alveolar epithelial and endothelial repair in ARDS.

ARDS is a life-threatening lung disease marked by severe AECS and ECs damage, causing rapid lung function loss and high mortality. MSCs are promising therapies due to their immunoregulatory and regenerative properties. While early studies highlighted MSCs' anti-inflammatory effects in ARDS, recent findings emphasize their essential role in repairing the AECs and ECs. In this review, we detail the molecular mechanisms and synergistic effects of MSCs in epithelial and endothelial repair. We also examine how MSC-mediated immune regulation intersects with tissue repair, explore new combination approaches using drugs, gene editing, and bioengineering, and outline clinical limitations and ongoing challenges. Patient heterogeneity, disease stage, treatment timing, and safety issues limit the conduct of clinical trials and their translation. We summarize the roles, limitations, and challenges of MSCs in ARDS to guide future research and inform the development of new treatments.