Extracellular Vesicles Derived from Adipose Mesenchymal Stem Cells Alleviate PM2.5-Induced Lung Injury and Pulmonary Fibrosis.

BACKGROUND Exposure to PM2.5 (fine particulate matter ≤2.5 μm in aerodynamic diameter) in air increases the risk of lung injury and pulmonary fibrosis (PF). Extracellular vesicles (EVs) derived from adipose mesenchymal stem cells (ADSCs) have been identified as a potential treatment based on the proteins or RNAs delivery and immunomodulatory properties. Here, we assessed the protective effects and mechanisms of ADSCs-EVs on PM2.5-induced lung injury or PF. MATERIAL AND METHODS Rats (male, 6 weeks old) were exposed to PBS or PM2.5 (1.5 mg/kg/day) for 3 days a week for 4 weeks. ADSCs-EVs were extracted by ultracentrifugation. PBS and ADSCs-EVs were administrated through intratracheal instillation. After the end of exposure, the rats were anesthetized and killed. Lung tissues with different treatments were collected for Western blot analysis and HE, IHC, and IF staining analysis. Cells exposed to PM2.5 or "PM2.5+ADSCs-EVs" in vitro were also collected for further Western blotting, qRT-PCR, and IF staining evaluation. RESULTS The results indicated that the initial response of lungs exposed to PM2.5 was lung injury with oxidative stress and inflammation. Long-term PM2.5 exposure resulted in obvious PF in rats. Treatment with ADSCs-EVs decreased PM2.5-induced apoptosis and necrosis in type II alveolar epithelial cells and alleviated lung injury and PF in rats. ADSCs-EVs suppressed reactive oxygen species (ROS) levels and inflammation induced by PM2.5. Furthermore, ADSCs-EVs inhibited TGF-ßRI by transferring let-7d-5p and further mitigated PF. CONCLUSIONS Our results suggest that EVs derived from ADSCs can alleviate PM2.5-induced lung injury and PF.