Abstract
Bronchopulmonary dysplasia (BPD) is a devastating lung condition that develops in premature newborns exposed to prolonged mechanical ventilation and supplemental oxygen. Significant morbidity and mortality are associated with this costly disease and effective therapies are limited. Mesenchymal stem/stromal cells (MSCs) are multipotent cells that can repair injured tissue by secreting paracrine factors known to restore the function and integrity of injured lung epithelium and endothelium. Most preclinical studies showing therapeutic efficacy of MSCs for BPD are administered either intratracheally or intravenously. The purpose of this study was to examine the feasibility and effectiveness of human cord tissue‐derived MSC administration given via the intranasal route. Human umbilical cord tissue MSCs were isolated, characterized, and given intranasally (500 000 cells per 20 μL) to a hyperoxia‐induced rat model of BPD. Lung alveolarization, vascularization, and pulmonary vascular remodeling were restored in animals receiving MSC treatment. Gene and protein analysis suggest the beneficial effects of MSCs were attributed, in part, to a concerted effort targeting angiogenesis, immunomodulation, wound healing, and cell survival. These findings are clinically significant, as neonates who develop BPD have altered alveolar development, decreased pulmonary vascularization and chronic inflammation, all resulting in impaired tissue healing. Our study is the first to report the intranasal delivery of umbilical cord Wharton's jelly MSCs in experimental BPD is feasible, noninvasive, and an effective route that may bear clinical applicability.
Highlights
The most common cause of morbidity in premature neonates is a devastating lung disease known as bronchopulmonary dysplasia (BPD).[2]
Results of this study show, for the first time to the authors' knowledge, that the intranasal delivery of Mesenchymal stem/stromal cells (MSCs) for Bronchopulmonary dysplasia (BPD) is effective in restoring lung alveolar growth and vascular development
Proteins pertaining to fibrogenesis and anti-vascular processes were different between room air (RA) and BPD + MSC groups, there was no significant difference between the BPD and BPD + MSC groups
Summary
Preterm birth is a major health concern affecting approximately 12% of all deliveries in the United States and costing over $26 billion every year.[1]. The most common cause of morbidity in premature neonates is a devastating lung disease known as bronchopulmonary dysplasia (BPD).[2]. BPD is characterized by a simplification of lung development following long-term exposure to mechanical ventilation and supplemental oxygen, both essential treatments for extremely preterm neonates.[3,4]. Neonates who develop BPD are at increased risk for cognitive impairment, frequent hospitalizations, and lifelong cardiopulmonary disease.[5–7]. The pathophysiology of BPD is complex and encompasses multiple processes including inflammation, oxidative stress, abnormal vasculogenesis, and impaired lung repair.[8–10]. Effective treatment options are limited, leaving a vulnerable patient population with an unmet need to develop novel therapies BPD is characterized by a simplification of lung development following long-term exposure to mechanical ventilation and supplemental oxygen, both essential treatments for extremely preterm neonates.[3,4] Neonates who develop BPD are at increased risk for cognitive impairment, frequent hospitalizations, and lifelong cardiopulmonary disease.[5–7] The pathophysiology of BPD is complex and encompasses multiple processes including inflammation, oxidative stress, abnormal vasculogenesis, and impaired lung repair.[8–10] Effective treatment options are limited, leaving a vulnerable patient population with an unmet need to develop novel therapies
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