title: iPSC-derived mesenchymal stem cells exert SCF-dependent recovery of cigarette smoke-induced apoptosis/proliferation imbalance in airway cells.
abstract: Mesenchymal stem cells (MSCs) have emerged as a potential cell-based therapy for pulmonary emphysema in animal models. Our previous study demonstrated that human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) were superior over bone marrow-derived MSCs (BM-MSCs) in attenuating cigarette smoke (CS)-induced airspace enlargement possibly through mitochondrial transfer. This study further investigated the effects of iPSC-MSCs on inflammation, apoptosis, and proliferation in a CS-exposed rat model and examined the effects of the secreted paracrine factor from MSCs as another possible mechanism in an in vitro model of bronchial epithelial cells. Rats were exposed to 4% CS for 1 hr daily for 56 days. At days 29 and 43, human iPSC-MSCs or BM-MSCs were administered intravenously. We observed significant attenuation of CS-induced elevation of circulating 8-isoprostane and cytokine-induced neutrophil chemoattractant-1 after iPSC-MSC treatment. In line, a superior capacity of iPSC-MSCs was also observed in ameliorating CS-induced infiltration of macrophages and neutrophils and apoptosis/proliferation imbalance in lung sections over BM-MSCs. In support, the conditioned medium (CdM) from iPSC-MSCs ameliorated CS medium-induced apoptosis/proliferation imbalance of bronchial epithelial cells in vitro. Conditioned medium from iPSC-MSCs contained higher level of stem cell factor (SCF) than that from BM-MSCs. Deprivation of SCF from iPSC-MSC-derived CdM led to a reduction in anti-apoptotic and pro-proliferative capacity. Taken together, our data suggest that iPSC-MSCs may possess anti-apoptotic/pro-proliferative capacity in the in vivo and in vitro models of CS-induced airway cell injury partly through paracrine secretion of SCF.
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.|Department of Ophthalmology, The University of Hong Kong, Hong Kong.
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Sze C
authors.initials: SC
authors.lastname: Yeung
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.|Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong.
authors.forename: Mary S M
authors.initials: MS
authors.lastname: Ip
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.|Department of Ophthalmology, The University of Hong Kong, Hong Kong.|Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong.|Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong.
authors.forename: Qizhou
authors.initials: Q
authors.lastname: Lian
authors.affiliation: Department of Medicine, The University of Hong Kong, Hong Kong.|Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong.|Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong.|Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Judith C W
authors.initials: JC
authors.lastname: Mak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D012907:Smoking / Q000009:adverse effects*; D019089:Stem Cell Factor / Q000494:pharmacology*
chemical_list: D017077:Culture Media, Conditioned; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit
keywords: apoptosis; cigarette smoke; mesenchymal stem cell; proliferation; stem cell factor