Intranasal delivery of human umbilical cord Wharton's jelly mesenchymal stromal cells restores lung alveolarization and vascularization in experimental bronchopulmonary dysplasia

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/...

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Bibliographic Details
Published in:	Stem cells translational medicine Vol. 9; no. 2; pp. 221 - 234
Main Authors:	Moreira, Alvaro, Winter, Caitlyn, Joy, Jooby, Winter, Lauryn, Jones, Maxwell, Noronha, Michelle, Porter, Melissa, Quim, Kayla, Corral, Alexis, Alayli, Yasmeen, Seno, Tyrelle, Mustafa, Shamimunisa, Hornsby, Peter, Ahuja, Sunil
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-02-2020 Oxford University Press
Subjects:	Administration, Intranasal Alveoli Analysis Angiogenesis Animals Animals, Newborn Bronchopulmonary dysplasia Bronchopulmonary Dysplasia - physiopathology Bronchopulmonary Dysplasia - therapy Cell survival Cells, Cultured Disease Models, Animal Dysplasia Endothelium Epithelium Fetal and Neonatal Stem Cells Health aspects Humans Hyperoxia Immunomodulation Infant, Newborn intranasal delivery Laboratory animals Lung - metabolism Lung diseases Lungs Mechanical ventilation Mesenchymal stem cells Mesenchymal Stem Cells - metabolism mesenchymal stromal cell Mesenchyme Morbidity neonate Neonates Ostomy Paracrine signalling Rats Recovery of function Rodents Scientific equipment and supplies industry Stem cells Stromal cells Umbilical cord Umbilical Cord - transplantation Vascularization Wharton Jelly - transplantation Wound healing United States Germany Belgium intranasal delivery neonate mesenchymal stromal cell bronchopulmonary dysplasia umbilical cord
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Summary:	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. Intranasal delivery of human umbilical cord mesenchymal stromal cells improves lung growth and development in a rat model mimicking neonatal lung disease.
Bibliography:	Funding information Francis Family Foundation; UTHSCSA School of Medicine Clinical Investigator Kickstart Pilot Grant; National Institutes of Health, Grant/Award Number: KL2TR001118 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 Funding information Francis Family Foundation; UTHSCSA School of Medicine Clinical Investigator Kickstart Pilot Grant; National Institutes of Health, Grant/Award Number: KL2TR001118
ISSN:	2157-6564 2157-6580 2157-6580
DOI:	10.1002/sctm.18-0273