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Isolation of CD146+ Resident Lung Mesenchymal Stromal Cells from Rat Lungs
Published on: June 17, 2016
Oxygen and mechanical ventilation impede the functional properties of resident lung mesenchymal stromal cells
Alvaro G Moreira1, Sartaj K Siddiqui1, Rolando Macias1
1Division of Neonatology, Department of Pediatrics, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
Insights
Routine neonatal care, including oxygen and ventilation, negatively impacts lung mesenchymal stromal cells (L-MSCs) in preterm rabbits. These changes affect cell function and genomic profiles, potentially impairing tissue repair.
Area of Science:
- Neonatal physiology
- Mesenchymal stromal cell biology
- Respiratory medicine
Background:
- Mesenchymal stromal cells (MSCs) are crucial for tissue development, growth, and repair.
- The impact of neonatal intensive care interventions on endogenous lung MSCs (L-MSCs) in preterm infants is largely unknown.
- Understanding these effects is vital for optimizing care for premature neonates.
Purpose of the Study:
- To investigate the effects of short-term mechanical ventilation and oxygen exposure on L-MSCs from preterm rabbits.
- To characterize changes in L-MSC biological properties and gene expression following neonatal care simulations.
Main Methods:
- Preterm rabbits were divided into fetal, spontaneous breathing (SB) with 50% O2, and mechanical ventilation (MV) with 50% O2 groups.
- L-MSCs were isolated and analyzed for differentiation capacity, colony formation, vascular endothelial growth factor (VEGF) mRNA expression, and gene expression profiles.
- Cellular morphology, including mitochondrial and endoplasmic reticulum structure, was examined.
Main Results:
- L-MSCs from the MV group exhibited reduced differentiation capacity and colony-forming ability.
- VEGF mRNA expression was lower in L-MSCs from the MV group.
- Significant genomic alterations were observed in L-MSCs from both SB and MV groups, affecting cell cycle and angiogenesis pathways; cellular ultrastructure changes were also noted.
Conclusions:
- Short-term exposure to hyperoxia and mechanical ventilation post-birth significantly alters the biological characteristics of L-MSCs.
- These alterations include impaired functional properties and substantial genomic changes.
- The observed modifications in L-MSCs may compromise their regenerative potential in preterm neonates.
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.

