Airway stem cells

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.

Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro

“…Dysregulation of airway epithelial basal cells can cause the aberrant remodeling process (e.g., basal cell hyperplasia, goblet cell hyperplasia, and squamous metaplasia)213. Our previous study found that p63 expression levels were higher in epithelium from patients with NP than in healthy controls, and it was associated with the severity of epithelial hyperplasia4.…”

“…Emerging evidence has demonstrated that epithelium from NP patients plays an important role in the pathogenesis of NP. In patients with NP, the epithelium is attacked by various stimulants, leading to acute or chronic injury and dysregulated restitution followed by aberrant remodeling2. Our previous studies reported a down-regulation of activator protein 1 (AP1) and its related genes (e.g., COX2, IL6, and epidermal growth factors) was associated with the damage of epithelial structure3; while up-regulation of p63 in basal cells was implicated in the epithelial hyperplasia in NP4.…”

Nasal Polyposis: Insights in Epithelial-Mesenchymal Transition and Differentiation of Polyp Mesenchymal Stem Cells

“…Basal cells have been identified as stem/progenitor cells able to self-renew and differentiate into other epithelial cell types [ 26 ]. Stem/progenitor cells have a central role in tissue homeostasis, repair and regeneration of mucous membrane including the nasal mucosa [ 27 ]. The cellular pathogenesis of nasal polyps is related to a homeostatic imbalance between the reduction in proliferation of nasal epithelial stem/progenitor cells [ 28 ], and the presence and differentiation of mesenchymal stem/progenitor cells (MSCs) [ 29 ].…”

Airway epithelial barrier dysfunction in the pathogenesis and prognosis of respiratory tract diseases in childhood and adulthood

“…3 This supports the claim that the nasal epithelium is exposed to all environmental agents including infectious agents (such as viruses, bacteria, and fungi), allergens, and air contaminants before the bronchial epithelium, thus protecting the lower airway. 3,4 However, some infectious agents, allergens, and air contaminants may still reach the lower airway. Therefore, both the upper and lower airways must have a functionally adequate epithelial barrier to ensure our survival.…”