Anti-fibrotic effects of bone morphogenetic protein-7-modified bone marrow mesenchymal stem cells on silica-induced pulmonary fibrosis

Abstract

Silicosis is an occupational lung disease caused by exposure to small particles of crystalline silica, which ultimately results in diffuse pulmonary fibrosis. Evidence indicates an anti-fibrotic role of bone morphogenetic protein-7 (BMP-7) and bone marrow mesenchymal stem cells (BMSCs) in lung diseases. Therefore, strategies incorporating genetic engineering and stem cell biology might have a tremendous potential to treat critical injuries and diseases. Therefore, we modified BMSCs to overexpress the BMP-7 gene (BMP-7-BMSCs) by lentivirus transduction, and then evaluated whether fibrotic processes were inhibited by these cells in vivo. Wistar rats were divided into four groups: control, silica, BMSCs, and BMP-7-BMSCs. The control group received saline, the silica group received silica and saline, the BMSCs group received silica and BMSCs, and the BMP-7-BMSCs group received silica and BMP-7-BMSCs. Rats were sacrificed on days 15 or 30 after silica instillation. Hematoxylin and eosin, and Masson's trichrome staining were performed for histological examination. The severity of fibrosis was evaluated by the levels of hydroxyproline, fibronectin (FN), and transforming growth factor (TGF)-β1. Restoration of the alveolar epithelium was detected by the epithelial marker surfactant protein (SP)-C and aquaporin (AQP)-5. Histopathological results showed that BMP-7-BMSCs could remarkably block the progression of silica-induced fibrosis. Hydroxyproline, FN, and TGF-β1 contents in the BMP-7-BMSCs-treated group were significantly lower than those in the BMSCs group (P<0.05). Furthermore, the expression of SP-C and AQP-5 in the BMP-7-BMSCs-treated group was significantly higher than those in the BMSCs group (P<0.05). In conclusion, the pulmonary fibrosis induced by silica in rats was significantly reduced by treatment with BMP-7-BMSCs and BMSCs. The anti-fibrotic effect of BMSCs can be strengthened by BMP-7. Treatment with BMP-7-BMSCs might be a potential therapeutic intervention for silicosis.

Keywords: Bone marrow mesenchymal stem cells; Bone morphogenetic protein-7; Pulmonary fibrosis; Silicosis.