Umbilical cord blood-derived exosomes from healthy term pregnancies protect against hyperoxia-induced lung injury in mice.

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic, devastating disease primarily occurring in premature infants. To date, intervention strategies to prevent or treat BPD are limited. We aimed to determine the effects of umbilical cord blood-derived exosomes (UCB-EXOs) from healthy term pregnancies on hyperoxia-induced lung injury and to identify potential targets for BPD intervention. A mouse model of hyperoxia-induced lung injury was created by exposing neonatal mice to hyperoxia after birth until the 14th day post birth. Age-matched neonatal mice were exposed to normoxia as the control. Hyperoxia-induced lung injury mice were intraperitoneally injected with UCB-EXO or vehicle daily for 3 days, starting on day 4 post birth. Human umbilical vein endothelial cells (HUVECs) were insulted with hyperoxia to establish an in vitro model of BPD to investigate angiogenesis dysfunction. Our results showed that UCB-EXO alleviated lung injuries in hyperoxia-insulted mice by reducing histopathological grade and collagen contents in the lung tissues. UCB-EXO also promoted vascular growth and increased miR-185-5p levels in the lungs of hyperoxia-insulted mice. Additionally, we found that UCB-EXO elevated miR-185-5p levels in HUVECs. MiR-185-5p overexpression inhibited cell apoptosis, whereas promoted cell migration in HUVECs exposed to hyperoxia. The luciferase reporter assay results revealed that miR-185-5p directly targeted cyclin-dependent kinase 6 (CDK6), which was downregulated in the lungs of hyperoxia-insulted mice. Together, these data suggest that UCB-EXO from healthy term pregnancies protect against hyperoxia-induced lung injuries via promoting neonatal pulmonary angiogenesis partially by elevating miR-185-5p.