Human Adipose-Derived Mesenchymal Stem Cells Ameliorate Elastase-Induced Emphysema in Mice by Mesenchymal-Epithelial Transition.
Human Adipose-Derived Mesenchymal Stem Cells Ameliorate Elastase-Induced Emphysema in Mice by Mesenchymal-Epithelial Transition.
复制标题
DOI：
10.2147/copd.s324952
复制
发表时间：
2021
影响因子：
2.8
通讯作者：
Ito T
中科院分区：
文献类型：
--
作者：
Fujioka N;Kitabatake M;Ouji-Sageshima N;Ibaraki T;Kumamoto M;Fujita Y;Hontsu S;Yamauchi M;Yoshikawa M;Muro S;Ito T
慢性阻塞性肺疾病（COPD）是一个世界性的问题，因为它的高患病率和死亡率。然而，目前尚无根本性的治疗方法来改善COPD肺组织的病理改变。近年来，脂肪间充质干细胞（ADSCs）在再生医学领域引起了人们的关注，以修复受损器官。此外，在一些动物模型中已经报道了它们在治疗呼吸系统疾病中的效用。然而，ADSC改善慢性呼吸系统疾病（包括COPD）的详细机制仍有待阐明。我们研究了人ADSC（hADSC）是否改善弹性蛋白酶诱导的肺气肿，以及hADSC是否在COPD小鼠模型中分化为肺泡上皮细胞。将雌性SCID-beige小鼠（6周龄）根据其是否接受磷酸缓冲盐水或猪胰弹性蛋白酶的腹膜内注射，以及其是否在腹膜内注射后3天接受盐水或hADSC的静脉内注射分为以下四组：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，并比较了从弹性蛋白酶-hADSC组的肺分离的hADSC与生理盐水或弹性蛋白酶给药后28天的幼稚hADSC之间的基因表达。hADSC改善了COPD的发病机制，包括在小鼠弹性蛋白酶诱导的肺气肿模型中的平均线性截距和用力呼气容积。此外，在施用后25天，在弹性蛋白酶处理的小鼠的肺中观察到hADSC。这些细胞表达与间充质-上皮转变相关的基因和肺泡上皮细胞的表面标记物，例如TTF-1、β-连环蛋白和E-钙粘蛋白。hADSC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。
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. 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. 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. hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal–epithelial transition.