Airway basal stem cell derived extracellular vesicles promote lung repair in chronic obstructive pulmonary disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible damage to the airways, alveoli, and pulmonary microvasculature. As the third leading cause of death worldwide, COPD remains without effective therapies to halt or reverse structural lung damage. Regenerative approaches utilizing lung-resident stem/progenitor cells present a promising therapeutic strategy; however, the underlying molecular mechanisms remain incompletely understood. This study aimed to investigate whether the reparative effects of airway basal stem cells (BCs) in COPD are mediated, at least in part, through paracrine mechanisms involving BC-derived extracellular vesicles (BC-EVs). Methods: Lineage-tracing analysis was performed to determine the involvement of endogenous BCs in epithelial repair following COPD-related lung injury. Airway BCs were isolated, expanded Results: Lineage tracing revealed active participation of endogenous BCs in epithelial repair. Transplantation of Conclusions: Airway basal stem cells are essential for lung epithelial regeneration, and together with their extracellular vesicles, provide a promising therapeutic strategy for COPD. The reparative effects of BCs are partially mediated by BC-EVs, which promote alveolar structure remodeling. This study delineates how BCs ameliorate COPD-induced lung injury and highlights BC-EVs as a viable cell-free therapeutic candidate with strong translational potential.