人脂肪间充质干细胞通过间充质上皮转化改善弹性蛋白酶诱导的小鼠肺气肿。
Human Adipose-Derived Mesenchymal Stem Cells Ameliorate Elastase-Induced Emphysema in Mice by Mesenchymal-Epithelial Transition.
机构信息
Department of Respiratory Medicine, Nara Medical University, Kashihara, Nara, Japan.
Department of Immunology, Nara Medical University, Kashihara, Nara, Japan.
出版信息
Int J Chron Obstruct Pulmon Dis. 2021 Oct 8;16:2783-2793. doi: 10.2147/COPD.S324952. eCollection 2021.
PURPOSE
Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD.
METHODS
Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration.
RESULTS
hADSCs improved the pathogenesis of COPD, including the mean linear intercept and forced expiratory volume, in an elastase-induced emphysema model in mice. Furthermore, hADSCs were observed in the lungs of elastase-treated mice at 25 days after administration. These cells expressed genes related to mesenchymal-epithelial transition and surface markers of alveolar epithelial cells, such as TTF-1, β-catenin, and E-cadherin.
CONCLUSION
hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal-epithelial transition.
目的
慢性阻塞性肺疾病（COPD）是一种全球性问题，因为其发病率和死亡率都很高。然而，目前还没有根本性的治疗方法可以改善 COPD 肺部的病理变化。最近，脂肪来源的间充质干细胞（ADSCs）在再生医学领域受到关注，可用于修复受损器官。此外，在一些动物模型中已经报道了它们在治疗呼吸疾病中的应用。然而，ADSCs 改善包括 COPD 在内的慢性呼吸系统疾病的详细机制仍有待阐明。我们研究了人 ADSCs（hADSCs）是否可以改善弹性蛋白酶诱导的肺气肿，以及 hADSCs 是否可以在 COPD 小鼠模型中分化为肺泡上皮细胞。
方法
将雌性 SCID-beige 小鼠（6 周龄）分为以下四组：根据它们是否接受气管内注射磷酸盐缓冲液或猪胰弹性蛋白酶，以及是否在气管内注射后 3 天接受静脉注射生理盐水或 hADSCs；对照组、hADSC 组、弹性蛋白酶组和弹性蛋白酶-hADSC 组。我们评估了肺功能，评估了组织学变化，并比较了弹性蛋白酶-hADSC 组和生理盐水或弹性蛋白酶给药后 28 天分离的 hADSCs 的基因表达。
结果
hADSCs 改善了 COPD 的发病机制，包括在弹性蛋白酶诱导的肺气肿小鼠模型中的平均线性截距和用力呼气量。此外，在给药后 25 天在弹性蛋白酶处理的小鼠肺部观察到 hADSCs。这些细胞表达了与间充质上皮转化和肺泡上皮细胞表面标志物相关的基因，如 TTF-1、β-连环蛋白和 E-钙黏蛋白。
结论
hADSCs 通过间充质上皮转化分化为肺泡上皮细胞，具有改善 COPD 发病机制的潜力。
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