Oxygen and mechanical ventilation impede the functional properties of resident lung mesenchymal stromal cells.

Alvaro G Moreira,Rolando Macias,Teresa L Johnson-Pais,Shamimunisa B Mustafa,Sartaj K Siddiqui,Jonathon A L Gelfond,Margarita M Vasquez,Steven R Seidner,Desiree Wilson

doi:10.1371/journal.pone.0229521

Alvaro G Moreira, Rolando Macias + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0229521

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Abstract

Resident/endogenous mesenchymal stromal cells function to promote the normal development, growth, and repair of tissues. Following premature birth, the effects of routine neonatal care (e.g. oxygen support and mechanical ventilation) on the biological properties of lung endogenous mesenchymal stromal cells is (L-MSCs) is poorly understood. New Zealand white preterm rabbits were randomized into the following groups: (i) sacrificed at birth (Fetal), (ii) spontaneously breathing with 50% O2 for 4 hours (SB), or (iii) mechanical ventilation with 50% O2 for 4h (MV). At time of necropsy, L-MSCs were isolated, characterized, and compared. L-MSCs isolated from the MV group had decreased differentiation capacity, ability to form stem cell colonies, and expressed less vascular endothelial growth factor mRNA. Compared to Fetal L-MSCs, 98 and 458 genes were differentially expressed in the L-MSCs derived from the SB and MV groups, respectively. Gene ontology analysis revealed these genes were involved in key regulatory processes including cell cycle, cell division, and angiogenesis. Furthermore, the L-MSCs from the SB and MV groups had smaller mitochondria, nuclear changes, and distended endoplasmic reticula. Short-term hyperoxia/mechanical ventilation after birth alters the biological properties of L-MSCs and stimulates genomic changes that may impact their reparative potential.

Highlights

Every year upwards of 15,000 premature neonates are diagnosed with a devastating lung disease, known as bronchopulmonary dysplasia, (BPD) [1]
Representative images of lung mesenchymal stromal cells (L-Mesenchymal stromal cells (MSCs)) isolated from each group exhibited characteristic fibroblastlike, elongated, spindle-shaped morphology over a period of 7days in culture (Fig 1A; 2–4 days in culture and 1B; 5–7 days in culture and the enlarged images to the right of panel A)
We investigated whether exposure to hyperoxia and mechanical ventilation with supplemental oxygen for 4h modified the biological characteristics of resident MSCs isolated from the preterm rabbit lung

Summary

Introduction

Every year upwards of 15,000 premature neonates are diagnosed with a devastating lung disease, known as bronchopulmonary dysplasia, (BPD) [1]. BPD is a multifaceted disease, attributed to prolonged exposure to supplemental oxygen and mechanical ventilation [2]. Effects of hyperoxia and ventilation on L-MSCs play a role in the study design, data collection, analysis, decision to publication, or preparation of the manuscript. 2. AM: National Institutes of Health, National Center for Advancing Translational Sciences KL2 TR001118, www.nih.gov, sponsor did not play a role in the study design, data collection, analysis, decision to publication, or preparation of the manuscript; Parker B. Francis Foundation, www.francisfellowships.org, sponsor did not play a role in the study design, data collection, analysis, decision to publication, or preparation of the manuscript

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