iPSC-derived mesenchymal stem cells exert SCF-dependent recovery of cigarette smoke-induced apoptosis/proliferation imbalance in airway cells.
iPSC-derived mesenchymal stem cells exert SCF-dependent recovery of cigarette smoke-induced apoptosis/proliferation imbalance in airway cells.
复制标题
iPSC 衍生的间充质干细胞对香烟烟雾诱导的气道细胞凋亡/增殖失衡发挥 SCF 依赖性恢复作用
DOI：
10.1111/jcmm.12962
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发表时间：
2017-02
影响因子：
5.3
通讯作者：
Mak JC
中科院分区：
文献类型：
--
作者：
Li X;Zhang Y;Liang Y;Cui Y;Yeung SC;Ip MS;Tse HF;Lian Q;Mak JC
间充质干细胞（MSC）已成为肺气肿动物模型的潜在细胞治疗方法。我们先前的研究表明，人诱导多能干细胞衍生的MSC（iPSC-MSC）在减弱香烟烟雾（CS）诱导的可能通过线粒体转移的空域扩大方面上级骨髓衍生的MSC（BM-MSC）。本研究进一步研究了iPSC-MSC对CS暴露大鼠模型中炎症、凋亡和增殖的影响，并在支气管上皮细胞体外模型中检查了MSC分泌的旁分泌因子的影响，这是另一种可能的机制。将大鼠暴露于4%CS，每天1小时，持续56天。在第29天和第43天，静脉内施用人iPSC-MSC或BM-MSC。我们观察到在iPSC-MSC处理后CS诱导的循环8-异前列烷和细胞因子诱导的中性粒细胞趋化因子-1的升高的显著减弱。同样，iPSC-MSC在改善CS诱导的巨噬细胞和嗜中性粒细胞浸润以及肺切片中细胞凋亡/增殖失衡方面也观察到优于BM-MSC的上级能力。作为支持，来自iPSC-MSC的条件培养基（CdM）在体外改善了CS培养基诱导的支气管上皮细胞的凋亡/增殖失衡。来自iPSC-MSC的条件培养基含有比来自BM-MSC的更高水平的干细胞因子（SCF）。从iPSC-MSC-衍生的CdM中去除SCF导致抗凋亡和促增殖能力的降低。综上所述，我们的数据表明，iPSC-MSCs可能在CS诱导的气道细胞损伤的体内和体外模型中部分通过旁分泌SCF具有抗凋亡/促增殖能力。
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.