Abstract
Backgroundc-Kit + lung stem cells have been described in the human healthy lung. Their potential relation with smoking and/or chronic obstructive pulmonary disease (COPD) is unknown.MethodsWe characterized and compared c-Kit+ cells in lung tissue of 12 never smokers (NS), 15 smokers with normal spirometry (S) and 44 COPD patients who required lung resectional surgery. Flow cytometry (FACS) was used to characterize c-Kit+ cells in fresh lung tissue disaggregates, and immunofluorescence (IF) for further characterization and to determine their location in OCT- embedded lung tissue.ResultsWe identified 4 c-Kit+ cell populations, with similar proportions in NS, S and COPD: (1) By FACS, c-Kithigh/CD45+ cells (4.03 ± 2.97% (NS), 3.96 ± 5.30% (S), and 5.20 ± 3.44% (COPD)). By IF, these cells were tryptase+ (hence, mast cells) and located around the airways; (2) By IF, c-Kitlow/CD45+/triptase- (0.07 ± 0.06 (NS), 0.03 ± 0.02 (S), and 0.06 ± 0.07 (COPD) cells/field), which likely correspond to innate lymphoid cells; (3) By FACS, c-Kitlow/CD45-/CD34+ (0.95 ± 0.84% (NS), 1.14 ± 0.94% (S) and 0.95 ± 1.38% (COPD)). By IF these cells were c-Kitlow/CD45-/CD31+, suggesting an endothelial lineage, and were predominantly located in the alveolar wall; and, (4) by FACS, an infrequent c-Kitlow/CD45-/CD34- population (0.09 ± 0.14% (NS), 0.08 ± 0.09% (S) and 0.08 ± 0.11% (COPD)) compatible with a putative lung stem cell population. Yet, IF failed to detect them and we could not isolate or grow them, thus questioning the existence of c-Kit+ lung stem-cells.ConclusionsThe adult human lung contains a mixture of c-Kit+ cells, unlikely to be lung stem cells, which are independent of smoking status and/or presence of COPD.
Highlights
The mechanisms of lung repair and regeneration are not fully understood [1, 2]
The adult human lung contains a mixture of c-Kit+ cells, unlikely to be lung stem cells, which are independent of smoking status and/or presence of Chronic obstructive pulmonary disease (COPD)
Characterization and location of lung c-kit+ cells In keeping with some similar previous studies in cardiac tissue [4, 5, 7, 8, 17], we found that the adult human lung contains a heterogeneous mixture of distinct c-Kit+ cell populations: (1) the majority of them (85% by IF) are mast cells, since c-Kithigh/CD45+ cells detected by Flow cytometry (FACS) expressed the specific mast cell marker tryptase in IF [18], and were mainly located around the intestitium
Summary
A population of putative lung stem cells characterized by the surface expression of the c-Kit receptor (c-Kit+, known as CD117) and the absence of hematopoietic, mesenchymal or epithelial cell markers, capable to repair the lung parenchyma in a Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide [9]. López-Giraldo et al BMC Pulmonary Medicine (2018) 18:123 mechanisms may be deficient in smokers with COPD. To test this hypothesis we: (1) carefully characterized the phenotype of pulmonary cells expressing c-Kit; (2) located stem cells (c-Kit+CD45-) cells in the lung parenchyma; and (3) compared their number and location in never smokers and smokers with or without COPD
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