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Epithelial stem cell populations are thought to exist in anatomically and functionally distinct locations within the lung, as suggested by earlier observations of lung injury models. This observational study looked at mouse models to support the hypotheses that stem cell populations exist in the distal lung, that these stem cells act to maintain bronchiolar Clara and alveolar cells, and that their transformation may give rise to lung adenocarcinomas.
In adult mice, bronchioalveolar stem cells (BASC) were identified at the bronchioalveolar duct junction (BADJ) within the terminal bronchioles by specific cell markers. These cell markers were distinct to Clara (CCA), alveolar (SP-C), and stem cell populations (Sca-1), and cells positive for all three markers at the BADJ were classified as BASC.
Direct effects of naphthalene (specific ablation of Clara cells) and bleomycin (specific alveolar damage) treatment on cell lineages were observed. BASC were shown to increase significantly in number 1 week following naphthalene treatment (p = 0.03) and 2 weeks following bleomycin treatment (p = 0.01). Proliferation of the BASC population was felt to directly mirror the increase in epithelial repair required secondary to the ablated Clara and alveolar cell populations.
Clara and alveolar type 2 cells are widely thought to be the precursor cells in lung adenocarcinomas. In this study, mouse models (Lox-K-Ras mice) showed that BASC numbers were increased, even in the earliest tumorigenic lesions (adenomas), and increased further during tumour progression. These findings support the existence of stem cell populations within the distal lung. The observed proliferation of BASC during epithelial repair in vivo, linkage to lung tumours, and properties of self-renewal and multipotent differentiation in culture are all important features of stem cell populations that were observed in the proposed BASC population.
Identification of bronchioalveolar stem cells in future studies may permit directed differentiation of these cells, allowing regeneration of defective epithelium in chronic lung diseases. It may also allow more effective early identification of lung carcinomas with the opportunity for directed treatment strategies against hyperproliferating BASC. Further work is required to elucidate the role of BASC in adenocarcinomas of the lung.
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