Oxygen Disrupts Human Fetal Lung Mesenchymal Cells. Implications for Bronchopulmonary Dysplasia
- 1 May 2019
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 60 (5), 592-600
- https://doi.org/10.1165/rcmb.2018-0358oc
Abstract
Rationale and Objectives: Exogenous mesenchymal stromal cells ameliorate experimental bronchopulmonary dysplasia. Moreover, data from term-born animal models and human tracheal aspirate-derived cells suggests altered mesenchymal signaling pathways in the pathophysiology of neonatal lung disease. Here, we sought to determine if tissue-resident human fetal lung mesenchymal cells contribute to normal and oxygen-impaired lung development, thus linking endogenous mesenchymal (dys-)function and exogenous mesenchymal cell repair activity. Methods: Mesenchymal cells were isolated from human fetal lung tissue (16-18 weeks of gestation), characterized and cultured in conditions resembling either intrauterine (5% O2) or extrauterine (21% and 60% O2) atmospheres. Secretome-data was compared to mesenchymal stromal cells obtained from term umbilical cord tissues. Measurements and Main Results: The human fetal lung’s mesenchyme almost exclusively contains CD146pos. mesenchymal stromal cells expressing SOX-2 and Oct-4, that secrete elastin, fibroblast growth factors 7 and 10, vascular endothelial growth factor, angiogenin and other lung-cell protecting/maturing proteins. Exposure to extrauterine atmospheres in vitro leads to excessive proliferation, reduced colony-forming ability and alterations in the cell’s surface marker profile. Reduction of elastin deposition and impaired secretion of lung cell protecting and -maturing proteins was noted. Conversely, umbilical cord-derived mesenchymal stromal cells abundantly secreted factors that impaired lung mesenchymal stromal cells lack to produce. Conclusions: In vitro-evidence for a contribution of human fetal lung mesenchymal stromal cells to normal and oxygen-impaired lung development is presented. Exogenous mesenchymal stromal cells may act by triggering signaling pathways prematurity-impaired endogenous mesenchymal cells lack to control.Keywords
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