@article{Bhavsar:2018:10.1016/j.jaci.2017.08.017,
author = {Bhavsar, PK and li, X and michaeloudes, C and Zhang, Y and Wiegman, C and Adcock, I and Lian, Q and Mak, J and Chung, KF},
doi = {10.1016/j.jaci.2017.08.017},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1634--1645.e5},
title = {Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways.},
url = {http://dx.doi.org/10.1016/j.jaci.2017.08.017},
volume = {141},
year = {2018}
}

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TY  - JOUR
AB  - BackgroundOxidative stress–induced mitochondrial dysfunction can contribute to inflammation and remodeling in patients with chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells.ObjectiveWe sought to examine the effect of induced pluripotent stem cell–derived mesenchymal stem cells (iPSC-MSCs) on oxidative stress–induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo.MethodsASMCs were cocultured with iPSC-MSCs in the presence of cigarette smoke medium (CSM), and mitochondrial reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), and apoptosis were measured. Conditioned medium from iPSC-MSCs and transwell cocultures were used to detect any paracrine effects. The effect of systemic injection of iPSC-MSCs on airway inflammation and hyperresponsiveness in ozone-exposed mice was also investigated.ResultsCoculture of iPSC-MSCs with ASMCs attenuated CSM-induced mitochondrial ROS, apoptosis, and ΔΨm loss in ASMCs. iPSC-MSC–conditioned medium or transwell cocultures with iPSC-MSCs reduced CSM-induced mitochondrial ROS but not ΔΨm or apoptosis in ASMCs. Mitochondrial transfer from iPSC-MSCs to ASMCs was observed after direct coculture and was enhanced by CSM. iPSC-MSCs attenuated ozone-induced mitochondrial dysfunction, airway hyperresponsiveness, and inflammation in mouse lungs.ConclusioniPSC-MSCs offered protection against oxidative stress–induced mitochondrial dysfunction in human ASMCs and in mouse lungs while reducing airway inflammation and hyperresponsiveness. These effects are, at least in part, dependent on cell-cell contact, which allows for mitochondrial transfer, and paracrine regulation. Therefore iPSC-MSCs show promise as a therapy for oxidative stress&
AU  - Bhavsar,PK
AU  - li,X
AU  - michaeloudes,C
AU  - Zhang,Y
AU  - Wiegman,C
AU  - Adcock,I
AU  - Lian,Q
AU  - Mak,J
AU  - Chung,KF
DO  - 10.1016/j.jaci.2017.08.017
EP  - 1645
PY  - 2018///
SN  - 0091-6749
SP  - 1634
TI  - Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways.
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2017.08.017
UR  - https://www.sciencedirect.com/science/article/pii/S0091674917314318?via%3Dihub
UR  - http://hdl.handle.net/10044/1/50757
VL  - 141
ER  - 

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