Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate acute lung injury partly mediated by hepatocyte growth factor.

Abstract

Several studies have highlighted the underlying role of mesenchymal stem cells microvesicles (MSC-MVs) in acute lung injury (ALI). Hepatocyte growth factor (HGF) derived from MSC-MVs is partly involved in their therapeutic effects; however, the detailed mechanism remains unclear. MVs were isolated from human Wharton's Jelly MSCs. The rat model of ALI was established by intratracheal instillation of bleomycin (BLM). A co-culture model of alveolar epithelial cells or pulmonary endothelial cells and MSC-MVs was utilized. Total protein content in bronchoalveolar lavage fluid (BALF) was determined by bicinchoninic acid method. White blood cell (WBC) and neutrophil in BALF were counted. ELISA was used for the determination of cytokines and HGF in BALF. Apoptosis was determined by TUNEL assay and Annexin V-FITC/PI staining as well as caspase-3 activity detection. HE and Masson staining of lung tissues was used for histopathology analysis. The expression of HGF and proteins involved in the PI3K/AKT/mTOR pathway were measured by quantitative Real-Time PCR (qRT-PCR) and western blotting. Treatment with MSC-MVs significantly inhibited BLM-induced apoptosis and fibrosis in lung tissues and PI3K/AKT/mTOR activation, which was reversed by HGF mRNA deficient MVs. Intriguingly, these effects were completely abrogated by PI3K inhibitor. The therapeutic effect of MSC-MVs in ALI was partly mediated through HGF mRNA.