2023, Vol. 27 ›› Issue (6): 827-834

Inhalation of bone marrow mesenchymal stem cells-derived exosomes alleviates inflammatory injury in chronic obstructive pulmonary disease

Wang Min1, Yin Xiushan2, Wang Yingxi1, Zhang Yan1, Zhao Long1, Xia Shuyue1   

Abstract: BACKGROUND: Many studies have demonstrated that exosomes derived from bone marrow mesenchymal stem cells show strong repair and regeneration ability in various models of respiratory inflammation and disease injury, but there are few studies on chronic obstructive pulmonary disease, and no studies have applied aerosolized inhalation of exosomes in model experiments of chronic obstructive pulmonary disease.  
OBJECTIVE: To investigate the therapeutic effects of exosomes derived from rat bone marrow mesenchymal stem cells on inflammation and lung injury in rats with chronic obstructive pulmonary disease by aerosol inhalation, and to determine the optimal therapeutic dose.
METHODS:   Rat bone marrow mesenchymal stem cells were isolated and cultured in vitro, and exosomes were extracted and identified. The rat model of chronic obstructive pulmonary disease was established by lipopolysaccharide combined with smoking for 28 days. Then low dose (0.5×108 particles/kg), medium dose (1.0×108 particles/kg), and high dose (1.5×108 particles/kg) exosome aerosol treatment and exosome (1.5×108 particles/kg) were given by tail vein injection. The model group was atomized with 1 mL PBS, while the control group was not molded with 1 mL PBS. Continuous atomization or injection was conducted for 5 days, and the test was started on the second day after the last atomization or injection treatment. The lung function indexes were tested by small animal pulmonary function instrument. The levels of interleukin-1β and tumor necrosis factor-α in bronchoalveolar lavage fluid and serum were detected by ELISA. The changes of lung tissues were assessed histologically by hematoxylin-eosin staining and Masson staining.  
RESULTS AND CONCLUSION: (1) The exosomes of bone marrow mesenchymal stem cells showed elliptic double-membrane vesicles under transmission electron microscopy, which were typical cup-shaped. Particle size analysis indicated that the peak diameter of exosomes was 91.7 nm, accounting for 97.3%, and the particle concentration was 3.3×109 L-1. In addition, surface proteins CD9 and CD63 were highly expressed. (2) Compared with caudal vein injection of exosome, aerosol inhalation of exosome significantly improved lung function, collagen deposition and pathological changes of lung tissue in rats with chronic obstructive pulmonary disease, and significantly decreased the levels of interleukin-1β and tumor necrosis factor-α in bronchoalveolar lavage fluid and serum. The low exosome dose had the most significant therapeutic effect. (3) These results suggest that inhalation of exosomes from bone marrow mesenchymal stem cells can reduce inflammatory injury in chronic obstructive pulmonary disease and the optimal dose may be 0.5×108 particles/kg.
Key words: bone marrow mesenchymal stem cell, exosome, chronic obstructive pulmonary disease, atomization inhalation, inflammation, lung injury