Author:
Hazra Snehashis,Li Rui,Vamesu Bianca M.,Jilling Tamas,Ballinger Scott W.,Ambalavanan Namasivayam,Kandasamy Jegen
Abstract
AbstractOxidant 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.
Funder
National Heart, Lung, and Blood Institute
American Thoracic Society
Publisher
Springer Science and Business Media LLC
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