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Article: Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways

TitleMesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways
Authors
KeywordsMesenchymal stem cell
airway hyperresponsiveness
airway smooth muscle
apoptosis
chronic obstructive pulmonary disease
Issue Date2017
PublisherMosby, Inc. The Journal's web site is located at http://www.elsevier.com/locate/jaci
Citation
Journal of Allergy and Clinical Immunology, 2017, p. pii: S0091-6749(17)31431-8 How to Cite?
AbstractBACKGROUND: Oxidative 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. 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.
Persistent Identifierhttp://hdl.handle.net/10722/251863
ISSN
2017 Impact Factor: 13.258
2015 SCImago Journal Rankings: 5.513
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, X-
dc.contributor.authorMichaeloudes, C-
dc.contributor.authorZhang, Y-
dc.contributor.authorWiegman, CH-
dc.contributor.authorAdcock, IM-
dc.contributor.authorLian, Q-
dc.contributor.authorMak, JCW-
dc.contributor.authorBhavsar, PK-
dc.contributor.authorChung, KF-
dc.date.accessioned2018-03-21T07:57:38Z-
dc.date.available2018-03-21T07:57:38Z-
dc.date.issued2017-
dc.identifier.citationJournal of Allergy and Clinical Immunology, 2017, p. pii: S0091-6749(17)31431-8-
dc.identifier.issn0091-6749-
dc.identifier.urihttp://hdl.handle.net/10722/251863-
dc.description.abstractBACKGROUND: Oxidative 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. 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.-
dc.languageeng-
dc.publisherMosby, Inc. The Journal's web site is located at http://www.elsevier.com/locate/jaci-
dc.relation.ispartofJournal of Allergy and Clinical Immunology-
dc.rightsPosting accepted manuscript (postprint): © <year>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectMesenchymal stem cell-
dc.subjectairway hyperresponsiveness-
dc.subjectairway smooth muscle-
dc.subjectapoptosis-
dc.subjectchronic obstructive pulmonary disease-
dc.titleMesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways-
dc.typeArticle-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.emailMak, JCW: judithmak@hku.hk-
dc.identifier.authorityLian, Q=rp00267-
dc.identifier.authorityMak, JCW=rp00352-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jaci.2017.08.017-
dc.identifier.pmid28911970-
dc.identifier.hkuros287506-
dc.identifier.isiWOS:000432148200011-
dc.publisher.placeUnited States-

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