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The Glandular Stem/Progenitor Cell Niche in Airway Development and Repair

¹ Department of Anatomy and Cell Biology, ² Department of Internal Medicine, and ³ Center for Gene Therapy of Cystic Fibrosis and other Genetic Diseases, College of Medicine, University of Iowa, Iowa City, Iowa

Correspondence and requests for reprints should be addressed to John F. Engelhardt, Ph.D., Department of Anatomy and Cell Biology, University of Iowa School of Medicine, 51 Newton Road, Room 1-111 BSB, Iowa City, IA 52242. E-mail: john-engelhardt{at}uiowa.edu

ABSTRACT

Airway submucosal glands (SMGs) are major secretory structures that lie beneath the epithelium of the cartilaginous airway. These glands are believed to play important roles in normal lung function and airway innate immunity by secreting antibacterial factors, mucus, and fluid into the airway lumen. Recent studies have suggested that SMGs may additionally serve as a protective niche for adult epithelial stem/progenitor cells of the proximal airways. As in the case of other adult stem cell niches, SMGs are believed to provide the localized environmental signals required to both maintain and mobilize stem/progenitor cells, in the setting of normal cellular turnover or injury. Aberrant proliferation and differentiation of glandular stem/progenitor cells may be associated with several hypersecretory lung diseases, including chronic bronchitis, asthma, and cystic fibrosis. To better understand the molecular mechanisms that regulate the specification and proliferation of glandular stem/progenitor cells in lung diseases associated with SMG hypertrophy and hyperplasia, researchers have begun to search for the molecular signals and cell types responsible for establishing the glandular stem/progenitor cell niche, and to dissect how these determinants of the niche change in the setting of proximal airway injury and repair. Such studies have revealed certain similarities between stem/progenitor cell niches of the distal conducting airways and the SMGs of the proximal airways.

Key Words: stem cell niche • submucosal gland • airway • lung • development • repair