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

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, t...