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Am J Respir Cell Mol Biol. 2018 Dec 18. doi: 10.1165/rcmb.2018-0358OC. [Epub ahead of print]

Oxygen Disrupts Human Fetal Lung Mesenchymal Cells: Implications for Bronchopulmonary Dysplasia.

Author information

1
Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Neonatology and Pediatric Critical Care Medicine, Dresden, Saxony, Germany.
2
DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Saxony, Germany.
3
Sinclair Centre for Regenerative Medicine, The Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada.
4
The University of New Mexico, Division of Neonatology, Department of Pediatrics, Albuquerque, New Mexico, United States.
5
Ottawa Hospital Research Institute & CHEO Research Institute, Pediatrics, Ottawa, Ontario, Canada ; bthebaud@ohri.ca.

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.

PMID:
30562051
DOI:
10.1165/rcmb.2018-0358OC

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