Objective
We investigated the effects and mechanisms of mesenchymal stem cell (MSC-MVs) derived microvesicles on pulmonary fibrosis in acute respiratory distress syndrome (ARDS) mice models.
Methods
The MSC-MVs with low hepatocyte growth factor (HGF) expressions (siHGF-MSC-MVs) were obtained by Lentivirus transfection. The ARDS pulmonary fibrosis mice models were established by injecting them with lipopolysaccharide (LPS) three times, after which MSC-MVs or siHGF-MSC-MVs were injected via the tail veins of ARDS pulmonary fibrosis mice. Homing of MSC-MVs in lung tissues were investigated by near-infrared live imaging. Immunohistochemical, Western blot, enzyme linked immunosorbent assay (ELISA) and other methods were used to detect the expressions of pulmonary fibrosis-related proteins, and to compare the effects of MSC-MVs on pulmonary fibrosis and fibrosis-related indicators in ARDS pulmonary fibrosis mice models.
Results
After tail vein injection, the MSC-MVs gradually migrated and homed to damaged lung tissues in ARDS mice models. Treatment of pulmonary fibrosis mice with MSC-MVs significantly reduced the lung injury and pulmonary fibrosis scores. However, low expressions of HGF (siHGF-MSC-MVs) significantly inhibited the roles of MSC-MVs (p < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expressions of type I collagen antigen, type III collagen antigen, TGF-β and α-SMA proteins while the siHGF-MVs group exhibited significantly elevated expressions of the proteins. In addition, compared to the pulmonary fibrosis group, pulmonary compliance (Cydn) and PO2/FiO2 were significantly low in the MSC-MVs group, and the effects of MSC-MVs were significantly inhibited after low expressions of HGF (all p < 0.05).
Conclusion
The MSC-MVs inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.