Abstract
Bronchopulmonary dysplasia (BPD), caused by hyperoxia in newborns and infants, results in lung damage and abnormal pulmonary function. However, the current treatments for BPD are steroidal and pharmacological therapies, which cause neurodevelopmental impairment. Treatment with umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) is an efficient alternative approach. To prevent pulmonary inflammation in BPD, this study investigated the hypothesis that a key regulator was secreted by MSCs to polarize inflammatory macrophages into anti-inflammatory macrophages at inflammation sites. Lipopolysaccharide-induced macrophages co-cultured with MSCs secreted low levels of the inflammatory cytokines, IL-8 and IL-6, but high levels of the anti-inflammatory cytokine, IL-10. Silencing decorin in MSCs suppressed the expression of CD44, which mediates anti-inflammatory activity in macrophages. The effects of MSCs were examined in a rat model of hyperoxic lung damage. Macrophage polarization differed depending on the levels of decorin secreted by MSCs. Moreover, intratracheal injection of decorin-silenced MSCs or MSCs secreting low levels of decorin confirmed impaired alveolarization of damaged lung tissues by down-regulation of decorin. In tissues, a decrease in the anti-inflammatory macrophage marker, CD163, was observed via CD44. Thus, we identified decorin as a key paracrine factor, inducing macrophage polarization via CD44, a master immunoregulator in mesenchymal stem cells.
Highlights
Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants, results from supplemental oxygen and mechanical ventilation treatment, which can cause barotrauma, volutrauma, and oxygen toxicity [1,2,3]
We investigated the therapeutic effects of UCB-mesenchymal stem cells (MSCs) on BPD and the paracrine factors involved in macrophage polarization
CD44 knockdown in NR8383 rat alveolar macrophages reduced macrophage polarization when co-cultured with MSCs
Summary
Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants, results from supplemental oxygen and mechanical ventilation treatment, which can cause barotrauma, volutrauma, and oxygen toxicity [1,2,3]. To prevent pulmonary inflammation caused by mechanical ventilators, systemic corticosteroid treatment has been used and shown to reduce mortality [6,7]. Pharmacological therapies, such as caffeine, diuretics, bronchodilators, and vitamin A, have been used for the prevention and management of BPD. It remains unclear how steroids and other medications reduce BPD, due to uncertainties regarding the dosage, timing, and choice of medication
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
