Mesenchymal stem cells alleviate oxidative stress–induced mitochondrial dysfunction in the airways - 04/05/18
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Abstract |
Background |
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.
Le texte complet de cet article est disponible en PDF.Key words : Mesenchymal stem cell, chronic obstructive pulmonary disease, oxidative stress, airway smooth muscle, mitochondria, cigarette smoke, ozone, airway hyperresponsiveness, apoptosis, inflammation
Abbreviations used : AHR, ASMC, BAL, BM-MSC, CdM, COPD, CS, CSM, DMEM, FITC, iPSC-MSC, JC-1, ΔΨm, MSC, RL, ROS, TNT, TUNEL
Plan
Supported by project grants from the Imperial College Trust, the National Natural Science Fund of China (NSFC no. 81370140 to J.C.W.M.; STFGD no. 2015B020225001; RGC/GRF no. HKU17113816; and NSFC No. 31571407 to Q.L.), and the Respiratory Disease Biomedical Research Unit at the Royal Brompton NHS Foundation Trust and Imperial College London. K.F.C. is a Senior Investigator of the National Institute of Health Research, United Kingdom. |
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Disclosure of potential conflict of interest: I. M. Adcock has received grants from the Medical Research Council, the British Heart Foundation, the Dunhill Medical Trust, and U-BIOPRED and has received personal fees from Chiesi, GlaxoSmithKline, Boehringer Ingelheim, Vectura, and AstraZeneca. P. K. Bhavsar has received grants from GlaxoSmithKline. K. F. Chung has board memberships with GlaxoSmithKline, Novartis, AstraZeneca, Merck, Respivert, and Gilead; has received grants from GlaxoSmithKline and Pfizer; and has received payment for lectures from AstraZeneca, Merck, Boehringer Ingelheim, Novartis, and GlaxoSmithKline. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 5
P. 1634 - mai 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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