CXCR4 enhances the inhibitory effects of bone mesenchymal stem cells on lung cell apoptosis in a rat model of smoking-induced COPD

Abstract

Objective Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death worldwide, and treatments are unsatisfactory, resulting in a major economic burden. Cellular therapy is commonly used for lung disease. We investigated treatment with CXCR4-overexpressing BMSCs during COPD model establishment. Methods We extracted and purified BMSCs from SD rats. Apoptosis induced by COPD was established by cigarette smoke exposure. BMSCs were transplanted in vivo twice a month during model establishment, and alveolar rupture in the lung was assessed. Lung cell apoptosis was assessed by TUNEL analysis, and the concentrations of apoptotic proteins in the lungs were detected by Western blotting. Results We successfully isolated BMSCs and established CXCR4-overexpressing BMSCs. Continuous cigarette smoke exposure caused alveolar septal rupture: in the model group, the 1-month alveolar MLI was significantly lower than that at the third month (p < 0.05). In the third month, the alveolar MLIs of the control and CXCR4-BMSC groups were lower than those of the model group (control group p < 0.01, CXCR4-BMSC group p < 0.05), and as shown by TUNEL staining, the apoptosis rates of the control and CXCR4-BMSC groups were significantly lower than those of the model groups (p < 0.01). The levels of the apoptotic proteins cleaved caspase-8, cleaved caspase-3 and cleaved PARP-1 were higher in the model group than in the control group (p < 0.05) and significantly lower in the CXCR4-BMSC group than in the model group (p < 0.05). Conclusion Transplantation of CXCR4-overexpressing BMSCs during COPD model generation significantly inhibited apoptosis via the extrinsic apoptosis pathway.