Stem cells and pulmonary fibrosis: cause or cure?
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.
Centre for Respiratory Research, University College London, 5 University Street, London, UK.
Katrina
K
McNulty
Sam M
SM
Janes
D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000628:therapy; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
D051176:beta Catenin