iPSC ‐derived mesenchymal stem cells exert SCF ‐dependent recovery of cigarette smoke‐induced apoptosis/proliferation imbalance in airway cells

Mesenchymal stem cells ( MSC s) 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 MSC s ( iPSC ‐ MSC s) were superior over bone marrow–derived MSC s ( BM ‐ MSC s) in attenuating cigarette smoke ( CS )‐induced airspace enlargement possibly through mitochondrial transfer. This study further investigated the effects of iPSC ‐ MSC s on inflammation, apoptosis, and proliferation in a CS ‐exposed rat model and examined the effects of the secreted paracrine factor from MSC s 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 ‐ MSC s or BM ‐ MSC s 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 ‐ MSC s was also observed in ameliorating CS ‐induced infiltration of macrophages and neutrophils and apoptosis/proliferation imbalance in lung sections over BM ‐ MSC s. In support, the conditioned medium (CdM) from iPSC ‐ MSC s ameliorated CS medium‐induced apoptosis/proliferation imbalance of bronchial epithelial cells in vitro . Conditioned medium from iPSC ‐ MSC s contained higher level of stem cell factor ( SCF ) than that from BM ‐ MSC s. 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 ‐ MSC s 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 .