Lung stem cells - from an evolving understanding to a paradigm shift?

Mairéad Hayes,John G Laffey,Gerard F Curley

doi:10.1186/scrt82

Mairéad Hayes, John G Laffey + Show 1 more

Open Access

https://doi.org/10.1186/scrt82

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Abstract

The ideal cell type to regenerate an acutely injured or chronically diseased lung would be a stem cell population from the patient's own lung. Consequently, extensive research efforts have focused on identifying and characterizing endogenous lung stem cells. Advances in techniques to facilitate cell isolation, labelling and tracking in vivo to determine their fate have led to the identification of several putative stem cell niches. Recently, convincing evidence has emerged for a novel stem/progenitor cell population in the submucous glands of the cartilaginous airways. These findings support the concept that there is no classical stem cell 'hierarchy' but that different progenitor populations within spatially distinct lung regions regenerate the lung epithelium adjacent to its niche. Intriguingly, recent findings challenge this concept; it was reported that the human lung may contain a primitive stem cell capable of differentiating into multiple cells of both endodermal and mesodermal lineage and of regenerating the injured lung. This suggests that a classical stem cell hierarchy may, in fact, exist in the lung. Although caution is needed in interpreting these emerging findings, the implications for our current concepts regarding lung stem cells, the insights into lung repair and regeneration, and the potential therapeutic implications are considerable.

Highlights

Respiratory diseases such as chronic obstructive pulmonary disease, asthma pulmonary fibrosis, and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) confer an enormous disease burden
Lung development begins during the fifth gestational week with the formation of epithelial buds from the primordial endoderm which grow into the embryonic mesenchyme
The submucosal gland duct stem/progenitor cell Previous studies have suggested that SMGs might constitute a stem cell niche, and progenitor cells have been identified in the SMGs of other organs, including the breast and submandibular gland [13,14]

Summary

Introduction

Respiratory diseases such as chronic obstructive pulmonary disease, asthma pulmonary fibrosis, and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) confer an enormous disease burden. There is no evidence from lineage-tracing studies that the embryonic lung – or, any developing organ – contains a common progenitor for endodermal and mesodermal lineages [6,7]. This suggests that separate populations of stem/progenitor cells are necessary for the maintenance of the endodermal- and mesodermal-derived lung components.

Results

Conclusion