Lung Stem/Progenitor Cells: Regulatory Mechanisms of Behavior, Development and Regeneration

Ahmed Hk El-Hashash

doi:10.4172/2161-0940.1000119

Abstract

New insights have been added to identification and characterization of stem and progenitor cells in the lung over the last few years. The exploration of endogenous lung stem and progenitor cells holds promise for advancing our understanding of the biology of lung repair and regeneration mechanisms after injury. This will also help in the future use of stem cell therapy for the development of regenerative medicine approaches for the treatment of different lung diseases. In this concise review, we describe the main types of lung stem/progenitor cell populations as well as summarize recent research progress and accumulated information regarding the behavior, development and function of stem/progenitor cells in the lung, and factors controlling their repair/regeneration after injury as well as molecular mechanisms regulating lung stem/progenitor cell behavior during development.

Highlights

Stem cells are undifferentiated or ‘blank’ cells found in the human body that have the potential to self-renew and develop into many different cell types that carry out different functions and, are multipotent source of multiple cell lineages
Driscoll et al [18] has demonstrated that the expression of telomerase, a stem/progenitor cell marker, after acute oxygen injury is strongly up-regulated in Alveolar Epithelial Cells (AEC) during the recovery phase. These findings suggest that alveolar epithelial cells either contain a relatively large subpopulation of progenitors, or that the majority of alveolar epithelial cells can undergo reactivation into a progenitor-like state in response to injury cues [18]
Other studies demonstrated that epithelial FGF9 primarily affects epithelial branching, whereas mesothelial FGF9 and mesenchymal WNT2A are principally responsible for maintaining mesenchymal Fibroblast Growth Factor (FGF)-WNT/β-catenin signaling [35]

Summary

Introduction

Stem cells are undifferentiated or ‘blank’ cells found in the human body that have the potential to self-renew and develop into many different cell types that carry out different functions and, are multipotent source of multiple cell lineages. Some studies identified the variant Clara cell as an endogenous lung stem cell, which infrequently proliferate during steady state but are felt to be responsible for repopulating the distal airway epithelium in response to injury [19]. A recent hypothesis suggests that enhancement or protection of alveolar progenitor cell function may be a viable therapeutic option that could possibly be evaluated in clinical trials using small molecules such as inosine In support of this hypothesis, Buckley et al [33] has shown that both FGF7 and inosine treatment can ameliorate DNA damage in alveolar epithelial cells as well as enhancing mitochondrial protection and the ability of AEC to migrate and repair in an in vitro scratch assay. Other studies demonstrated that epithelial FGF9 primarily affects epithelial branching, whereas mesothelial FGF9 and mesenchymal WNT2A are principally responsible for maintaining mesenchymal FGF-WNT/β-catenin signaling [35]

Localization and characterization

Endogenous Mesenchymal Progenitors

Smooth muscle progenitors

Vascular progenitors