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© 2006 The American Thoracic Society
doi: 10.1513/pats.200605-117SF
Airway Epithelial Stem Cells and the Pathophysiology of Chronic Obstructive Pulmonary Disease
Departments of Cell and Molecular Physiology, and Medicine and Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Correspondence and requests for reprints should be addressed to Scott H. Randell, Ph.D., UNC CF Center, CB 7248, Room 4011, Thurston-Bowles Building, Chapel Hill, NC 27599. E-mail: randell{at}med.unc.edu
ABSTRACT
Characteristic pathologic changes in chronic obstructive pulmonary disease (COPD) include an increased fractional volume of bronchiolar epithelial cells, fibrous thickening of the airway wall, and luminal inflammatory mucus exudates, which are positively correlated with airflow limitation and disease severity. The mechanisms driving general epithelial expansion, mucous secretory cell hyperplasia, and mucus accumulation must relate to the effects of initial toxic exposures on patterns of epithelial stem and progenitor cell proliferation and differentiation, eventually resulting in a self-perpetuating, and difficult to reverse, cycle of injury and repair. In this review, current concepts in stem cell biology and progenitor–progeny relationships related to COPD are discussed, focusing on the factors, pathways, and mechanisms leading to mucous secretory cell hyperplasia and mucus accumulation in the airways. A better understanding of alterations in airway epithelial phenotype in COPD will provide a logical basis for novel therapeutic approaches.
Key Words: epithelium • hyperplasia • metaplasia • mucus hypersecretion • stem cells
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