Abstract | BACKGROUND: OBJECTIVE: We 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. METHODS: ASMCs 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. RESULTS: Coculture 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. CONCLUSION: iPSC-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-dependent lung diseases, such as COPD.
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Authors | Xiang Li, Charalambos Michaeloudes, Yuelin Zhang, Coen H Wiegman, Ian M Adcock, Qizhou Lian, Judith C W Mak, Pankaj K Bhavsar, Kian Fan Chung |
Journal | The Journal of allergy and clinical immunology
(J Allergy Clin Immunol)
Vol. 141
Issue 5
Pg. 1634-1645.e5
(05 2018)
ISSN: 1097-6825 [Electronic] United States |
PMID | 28911970
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Culture Media, Conditioned
- Reactive Oxygen Species
- Smoke
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Topics |
- Animals
- Apoptosis
(physiology)
- Coculture Techniques
(methods)
- Culture Media, Conditioned
(metabolism)
- Disease Models, Animal
- Humans
- Induced Pluripotent Stem Cells
(metabolism)
- Inflammation
(metabolism, pathology)
- Lung
(metabolism, pathology)
- Male
- Membrane Potential, Mitochondrial
(physiology)
- Mesenchymal Stem Cells
(metabolism, pathology)
- Mice
- Mice, Inbred C57BL
- Mitochondria
(metabolism, pathology)
- Mitochondrial Diseases
(metabolism, pathology)
- Myocytes, Smooth Muscle
(metabolism, pathology)
- Oxidative Stress
(physiology)
- Pulmonary Disease, Chronic Obstructive
(metabolism, pathology)
- Reactive Oxygen Species
(metabolism)
- Smoke
(adverse effects)
- Nicotiana
(adverse effects)
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