Centre for Respiratory Research, University College London, 5 University Street, London, UK.
Proc Am Thorac Soc. 2012 Jul;9(3):164-71. doi: 10.1513/pats.201201-010AW.
Pulmonary fibrosis is a feature of a number of important lung diseases, and alveolar epithelial injury plays a key role in their pathogenesis. Traditionally, type II alveolar epithelial cells have been viewed as the progenitor cells of the alveolar epithelium; however, recent studies have identified a number of other progenitor and stem cell populations that may participate in alveolar epithelial repair. These studies suggest that the injury microenvironment plays a role in regulation of progenitor cell populations. In human idiopathic pulmonary fibrosis, epithelial abnormalities including altered cell cycling characteristics, hyperplasia, and metaplasia are observed, suggesting that dysregulation of epithelial progenitor cells contributes to the characteristic aberrant repair process. Reactivation of developmental signaling pathways such as the Wnt-β-catenin pathway is implicated in the dysregulation of these cells, and targeting these pathways may provide opportunities for therapeutic intervention. There has been a great deal of interest in the delivery of exogenous stem cells as a therapeutic strategy, and various stem and progenitor cell populations have improved outcomes in animal lung fibrosis models. The contributions of these cells to alveolar epithelial regeneration have been variable, and secretion of soluble mediators has been implicated in the beneficial effects. It remains to be seen whether the promising results seen in the preclinical studies will translate to human disease, and the first studies using mesenchymal stem cells in clinical trials for fibrotic lung disease are underway. Strategies using other stem cell populations hold promise, but currently these are a lot further from the bedside.
肺纤维化是多种重要肺部疾病的特征，肺泡上皮损伤在其发病机制中起着关键作用。传统上，II 型肺泡上皮细胞被认为是肺泡上皮的祖细胞；然而，最近的研究已经确定了一些其他的祖细胞和干细胞群体，它们可能参与肺泡上皮修复。这些研究表明，损伤微环境在祖细胞群体的调节中起着作用。在特发性肺纤维化患者中，观察到上皮异常，包括细胞周期特征改变、增生和化生，表明上皮祖细胞的失调导致了特征性的异常修复过程。发育信号通路的重新激活，如 Wnt-β-catenin 通路，与这些细胞的失调有关，靶向这些通路可能为治疗干预提供机会。人们对作为治疗策略的外源性干细胞的输送非常感兴趣，各种干细胞和祖细胞群体已改善了动物肺纤维化模型的预后。这些细胞对肺泡上皮再生的贡献各不相同，可溶性介质的分泌与有益作用有关。目前尚不清楚临床前研究中看到的有希望的结果是否会转化为人类疾病，并且正在进行临床试验中使用间充质干细胞治疗纤维化肺部疾病的首次研究。使用其他干细胞群体的策略有希望，但目前这些策略离临床应用还有很长的路要走。
