Epithelial stem cells of the lung: privileged few or opportunities for many?

Abstract

Most reviews of adult stem cells focus on the relatively undifferentiated cells dedicated to the renewal of rapidly proliferating tissues, such as the skin, gut and blood. By contrast, there is mounting evidence that organs and tissues such as the liver and pancreatic islets, which turn over more slowly,use alternative strategies, including the self-renewal of differentiated cells. The response of these organs to injury may also reveal the potential of differentiated cells to act as stem cells. The lung shows both slow turnover and rapid repair. New experimental approaches, including those based on studies of embryonic development, are needed to identify putative lung stem cells and strategies of lung homeostasis and repair.

Stem Cells and Cell Therapies in Lung Biology and Diseases: Conference Report

“…He noted that most studies therefore focus on candidate endogenous progenitor or stem cells using models of adult lung injury and repair (7). Although these models provide important insights into the pathways and cellular activities involved in the lung's regenerative response, they may not necessarily reflect the behavior of the endogenous progenitors in the uninjured lung (8).…”

Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture

“…17 They are candidate stem cells in the conducting airways, responsible for normal cell replacement and epithelial remodeling upon lung injury. 18 Upon damage in airway epithelium, the basal cells show increased reactivity demonstrated by increased expression of p63, a basal cell restricted transcription factor and its downstream target cytokeratin 14 (CK14). 19,20 Recent studies have implicated p63 with EMT.…”

Elf3 plays a role in regulating bronchiolar epithelial repair kinetics following Clara cell-specific injury

“…After treatment with naphthalene, injured and necrotic Clara cells are replaced by other airway epithelial cells, which undergo dynamic changes in cell migration, proliferation, and differentiation. 1 Many different cell types have been shown to be involved in the process of airway epithelial regeneration following naphthalene-induced Clara cell ablation in mice, and those identified to date include: basal cells, 2,3 pulmonary neuroendocrine cells, [4][5][6] bronchioalveolar stem cells, 7,8 ciliated cells, 9,10 peribronchiolar interstitial cells, 11,12 and a pollutant-resistant sub-population of Clara cells that retain their expression of Clara cell 10-kDa secretory protein (CC10/CCSP), also known as variant CC10/CCSP-expressing (vCE) stem cells. [13][14][15] However, the role of various transcription factors in regulating the process of airway epithelial regeneration requires further investigation.…”