Lung epithelial stem cells

This review concentrates on recent evidence about lung stem cell origins and plasticity. The range of potential cells which can repopulate the injured lung, classically the basal and mucous secretory cells of the trachea, the Clara cells of the bronchiole, and the type II pneumocyte of the alveolus, has been extended to include the mucus-gland duct cells of the trachea and bronchus. Some evidence suggests that there are variant Clara cells that lack cytochrome P-450 and so are spared toxic activation of xenobiotics, and may aid bronchiolar repopulation after injury, such as with naphthalene. There may even be involvement of the neuroepithelial bodies or cells in this, though the evidence is not yet conclusive. The search for a resident pulmonary multipotent cell for repopulating any lung epithelium has not yet been successful. The picture remains similar to earlier conclusions, in that the local stem or precursor cell is the most likely to contribute to local needs in times of tissue damage. There remains a major challenge for lung cancer treatment, where high-dose chemo- or radio-therapy may be hoped to promote the seeding and repair of lung parenchyma by circulating bone marrow stem cells, as seen in liver models. Patient survival rates do not yet suggest that this occurs to any great extent, but this remains to be shown formally. The effects of prior fibrosis and tumour necrosis are probably confounding factors in this lack of rescue.