Airway stem cells: review of potential impact on understanding of upper airway diseases

Abstract

Epithelial remodeling is a part of our natural defense mechanisms, and includes migration, proliferation, and differentiation of epithelial cells, as well as the interactions between epithelial and stromal cells. It is not yet possible to distinguish between cause and effect during epithelium remodeling, and are there no clear roles for the many factors involved in respiratory infectious and inflammatory diseases due to a lack of critical information about epithelial cell responses. Most reported data are from lower airway studies or animal models. Therefore, research based on human nasal epithelial stem/progenitor cells can illuminate the pathophysiology of nasal airway disease from a different, more specific perspective. In this review, we discuss epithelial stem/progenitor cell research throughout the airway, with special attention to phenotypes and characterization of these cells from the nasal airway. Recently, we have isolated and cultured P63-positive human epithelial stem/progenitor cells from turbinate biopsies of healthy volunteers and from inflamed mucosa of patients with chronic rhinosinusitis with and without nasal polyposis. These cells propagate in serum-free, growth factor-supplemented, Dulbecco's modified Eagle's medium/F12 media, on either human fibroblast or 3T3 feeder layers. Self-renewal, proliferation, and differentiation potential at an air-liquid interface are being investigated to understand the molecular pathways underlying nasal inflammation. This in vitro culture system for nasal epithelial regeneration will allow molecular studies of human nasal epithelial cell interactions, differentiation, and repair, as well as responses to both environmental agents and to potential anti-inflammatory treatments.