Stem/Progenitor Cells in Lung Development, Injury Repair, and Regeneration
- 15 August 2008
- journal article
- review article
- Published by American Thoracic Society in Proceedings of the American Thoracic Society
- Vol. 5 (6), 703-706
- https://doi.org/10.1513/pats.200801-012aw
Abstract
At least two populations of epithelial stem/progenitor cells give rise to the lung anlage, comprising the laryngo-tracheal complex versus the distal lung below the first bronchial bifurcation. Amplification of the distal population requires FGF9-FGF10-FGFR2b-Sprouty signaling. Residual pools of adult stem cells are hypothesized to be the source of lung regeneration and repair. These pools have been located within the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction as well as within the alveolar epithelial surface. Rapid repair of the denuded alveolar surface after injury is clearly key to survival. Strategies to enhance endogenous alveolar epithelial repair could include protection of epithelial progenitors from injury and/or stimulation of endogenous progenitor cell function. Protection with inosine or FGF signaling are possible small molecule therapeutic options. Alternatively, exogenous stem/progenitor cells can be delivered into the lung either intravenously, intratracheally, or by direct injection. Sources of exogenous stem/progenitor cells that are currently under evaluation in the context of acute lung injury repair include embryonic stem cells, bone marrow- or fat-derived mesenchymal stem cells, circulating endothelial progenitors, and, recently, amniotic fluid stem/progenitor cells. Further work will be needed to translate stem/progenitor cell therapy for the lung.Keywords
This publication has 30 references indexed in Scilit:
- Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung CancerCell, 2005
- A novel function for the protein tyrosine phosphatase Shp2 during lung branching morphogenesisDevelopmental Biology, 2005
- Fgf10expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineageDevelopment, 2005
- In vivo inosine protects alveolar epithelial type 2 cells against hyperoxia-induced DNA damage through MAP kinase signalingAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Airway injury in lung disease pathophysiology: selective depletion of airway stem and progenitor cell pools potentiates lung inflammation and alveolar dysfunctionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004
- Apoptosis and DNA damage in type 2 alveolar epithelial cells cultured from hyperoxic rats.American Journal of Physiology-Lung Cellular and Molecular Physiology, 1998
- Fibroblast Growth Factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lungDevelopment, 1997
- Cell cycle in alveolar epithelial type II cells: integration of Matrigel and KGF.American Journal of Physiology-Lung Cellular and Molecular Physiology, 1997