Journal Article

Mesenchymal stem cell bioenergetics and apoptosis are associated with risk for bronchopulmonary dysplasia in extremely low birth weight infants

Hazra, Snehashis, Ambalavanan, Namasivayam, Li, Rui, Kandasamy, Jegen, Jilling, Tamas, Vamesu, Bianca M., Ballinger, Scott W.

2022

Overview

Oxidant stress contributes significantly to the pathogenesis of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants. Mitochondrial function regulates oxidant stress responses as well as pluripotency and regenerative ability of mesenchymal stem cells (MSCs) which are critical mediators of lung development. This study was conducted to test whether differences in endogenous MSC mitochondrial bioenergetics, proliferation and survival are associated with BPD risk in ELBW infants. Umbilical cord-derived MSCs of ELBW infants who later died or developed moderate/severe BPD had lower oxygen consumption and aconitase activity but higher extracellular acidification—indicative of mitochondrial dysfunction and increased oxidant stress—when compared to MSCs from infants who survived with no/mild BPD. Hyperoxia-exposed MSCs from infants who died or developed moderate/severe BPD also had lower PINK1 expression but higher TOM20 expression and numbers of mitochondria/cell, indicating that these cells had decreased mitophagy. Finally, these MSCs were also noted to proliferate at lower rates but undergo more apoptosis in cell cultures when compared to MSCs from infants who survived with no/mild BPD. These results indicate that mitochondrial bioenergetic dysfunction and mitophagy deficit induced by oxidant stress may lead to depletion of the endogenous MSC pool and subsequent disruption of lung development in ELBW infants at increased risk for BPD.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/136/532/2074 / 631/553/1464 / 631/80/642/333 / 692/699/1785 / 692/700/1720 / 692/700/1720/3185 / 692/700/1720/3186 / Acidification / Aconitate Hydratase - metabolism / Apoptosis / Bioenergetics / Birth Weight / Bronchopulmonary Dysplasia - etiology / Dysplasia / Energy Metabolism / Humanities and Social Sciences / Humans / Hyperoxia / Infant / Infant, Extremely Low Birth Weight / Infant, Newborn / Infants / Low birth weight / Lung diseases / Mesenchymal stem cells / Mesenchymal Stem Cells - metabolism / Mitochondria / multidisciplinary / Oxidants / Oxidants - metabolism / Oxidation / Oxidizing agents / Oxygen consumption / Pluripotency / Protein Kinases - metabolism / PTEN-induced putative kinase / Science / Science (multidisciplinary) / Stem cells / Umbilical cord