Journal Article

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

McConaghy, Suzanne, Freund, Daniel, Möbius, Marius A., Koss, Sarah, Vadivel, Arul, Rüdiger, Mario, Thébaud, Bernard, Ohls, Robin K.

2019

Overview

Exogenous mesenchymal stromal cells (MSCs) ameliorate experimental bronchopulmonary dysplasia. Moreover, data from term-born animal models and human tracheal aspirate–derived cells suggest altered mesenchymal signaling in the pathophysiology of neonatal lung disease. We hypothesized that hyperoxia, a factor contributing to the development of bronchopulmonary dysplasia, perturbs human lung–resident MSC function. Mesenchymal cells were isolated from human fetal lung tissue (16–18 wk of gestation), characterized and cultured in conditions resembling either intrauterine (5% O2) or extrauterine (21% and 60% O2) atmospheres. Secretome data were compared with MSCs obtained from term umbilical cord tissues. The human fetal lung mesenchyme almost exclusively contains CD146pos. MSCs expressing SOX-2 and OCT-4, which 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, alterations in the cell’s surface marker profile, decreased elastin deposition, and impaired secretion of factors important for lung growth. Conversely, umbilical cord–derived MSCs abundantly secreted factors that impaired lung MSCs are unable to produce. Oxygen-impaired human fetal lung MSC function may contribute to disrupted repair capacity and arrested lung growth. Exogenous MSCs may act by triggering the signaling pathways lost by impaired endogenous lung mesenchymal cells.

• Publisher: Oxford University Press
• Subject: Angiogenesis / Angiogenin / Animal models / Antibiotics / Bronchopulmonary Dysplasia / CD146 Antigen - genetics / CD146 Antigen - metabolism / Cell Proliferation - drug effects / Cell Survival - drug effects / Dysplasia / Elastin / Elastin - genetics / Elastin - metabolism / Fetus / Fetuses / Fibroblast Growth Factor 10 - genetics / Fibroblast Growth Factor 10 - metabolism / Fibroblast Growth Factor 7 - genetics / Fibroblast Growth Factor 7 - metabolism / Fibroblasts / Gene expression / Gene Expression Regulation - drug effects / Gestation / Gestational Age / Growth factors / Human subjects / Humans / Hyperoxia / Lung - drug effects / Lung - metabolism / Lung - pathology / Lung diseases / Lungs / Mesenchymal Stem Cells - drug effects / Mesenchymal Stem Cells - metabolism / Mesenchymal Stem Cells - pathology / Mesenchyme / Models, Biological / Neonates / Oct-4 protein / Octamer Transcription Factor-3 - genetics / Octamer Transcription Factor-3 - metabolism / Oxygen / Oxygen - toxicity / Paracrine Communication - drug effects / Penicillin / Primary Cell Culture / Ribonuclease, Pancreatic - genetics / Ribonuclease, Pancreatic - metabolism / Secretion / Secretome / Signal Transduction / SOXB1 Transcription Factors - genetics / SOXB1 Transcription Factors - metabolism / Stem cells / Stromal cells / Surface markers / Transplants & implants / Umbilical cord / Umbilical Cord - cytology / Umbilical Cord - drug effects / Umbilical Cord - metabolism / Vascular endothelial growth factor / Vascular Endothelial Growth Factor A - genetics / Vascular Endothelial Growth Factor A - metabolism