Abstract
Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy; however, there is no effective treatment for it. In the present study, a neonatal mouse BPD model was established by continuous exposure to high oxygen (HO) levels. Mice were divided randomly into 5 groups: control, BPD, EPO, MSCs, and MSCs+EPO. At 2 weeks post-treatment, vessel density and the expression levels of endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), and its receptor C-X-C chemokine receptor type 4 (CXCR4) were significantly increased in the MSC+EPO group compared with the EPO or MSCs group alone; moreover, EPO significantly enhanced MSCs proliferation, migration, and anti-apoptosis ability in vitro. Furthermore, the MSCs could differentiate into cells that were positive for the type II alveolar epithelial cell (AECII)-specific marker surfactant protein-C, but not positive for the AECI-specific marker aquaporin 5. Our present results suggested that MSCs in combination with EPO could significantly attenuate lung injury in a neonatal mouse model of BPD. The mechanism may be by the indirect promotion of angiogenesis, which may involve the SDF-1/CXCR4 axis.
Highlights
Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in preterm infants requiring mechanical ventilation and oxygen therapy [1], and is characterized by restricted lung growth and subdued alveolar and blood vessel development; the structural development of the alveoli is blunted as a consequence of inflammation and oxygen toxicity [2, 3]
Hematoxylin and eosin-stained sections of lung tissue demonstrated that alveolar structure was markedly abnormal after neonatal mice were exposed to high oxygen for 14 days (Figure 1B), degree of alveolarization measured by radial alveolar counts (Figure 1C) and alveolar septum thickness (Figure 1D) were significantly improved in the mesenchymal stem/stromal cells (MSCs), EPO and MSCs+EPO groups compared with BPD group, especially in the MSCs+EPO group (P < 0.05)
Data are presented as the mean ± standard deviation (SD). *P < 0.05 compared with the control group; #P < 0.05 compared with the BPD group; ᇞP
Summary
Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease in preterm infants requiring mechanical ventilation and oxygen therapy [1], and is characterized by restricted lung growth and subdued alveolar and blood vessel development; the structural development of the alveoli is blunted as a consequence of inflammation and oxygen toxicity [2, 3]. A large number of studies [4,5,6] have shown that stem cell-based therapies, such as mesenchymal stem/stromal cells (MSCs), are promising approaches in preclinical models for the prevention and/or treatment of BPD and other major sequelae of preterm birth. The influence of combination therapy with EPO and MSCs on angiogenesis in BPD and the underlying mechanism are not fully clear; the present study was performed to examine these issues
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