Abstract 18655: Lung Stem Cells and Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, enlargement of bronchioles and alveoli, destruction of the alveolar walls, and ultimately respiratory failure. The recognition that the distal airways contain a pool of c-kit-positive lung stem cells (LSCs) suggests that the adverse evolution of COPD may be mediated by a decrease in LSCs and their ability to restore organ integrity. To test this hypothesis, the number and phenotypic properties of LSCs from control (N=13) and COPD (N=7) lungs were determined to establish a potential relationship between stem cell growth and differentiation and the pathobiology of the disease. We identified that the compartment of c-kit-positive LSCs contains a cell population that does not express the mesenchymal epitopes CD44/CD73/CD105, i.e., non-mesenchymal LSCs (non-mLSCs) and a cell class that is positive for these epitopes, i.e., mesenchymal-like LSCs (mLSCs). In control lungs, 77% of c-kit-positive cells were non-mLSCs and 23% were mLSCs. With COPD, however, the proportion of non-mLSCs, 49%, and mLSCs, 51%, was comparable, resulting in an increase in the pool of mLSCs and a decrease in the fraction of non-mLSCs; the loss of this balance may contribute to lung pathology. Importantly, non-mLSCs generated type-1 and type-2 alveolar epithelial cells and capillary endothelial cells, while mLSCs failed to form these specific cell types. The components of the gas exchange units appear to be under the control of a multipotent non-mLSC which, in a coordinated manner, regulates the structures responsible for the gas transfer across the epithelial-endothelial barrier. Because of the controversy in the field, the relevance of lung c-kit-positive cells was ascertained by lineage tracing in mice. The fate mapping strategy clearly documented that c-kit-positive cells differentiate into type-1 and type-2 alveolar epithelial cells and capillary endothelial cells, strengthening the observations in humans. Thus, the c-kit epitope distinguishes a class of stem/progenitor cells which differentiate into structures of endodermal and mesodermal origin, and the delivery of this class of non-mLSCs may have therapeutic importance in patients with COPD and hypoxemic respiratory failure.
Author Disclosures: A. Czarna: None. Y. Sakairi: None. A. Matsuda: None. K.E. Hatzistergos: None. X. Liu: None. M. Luciani: None. L. Graciotti: None. A. Di Rocco: None. T. Hosoda: None. R. Bueno: None. P.C. Camp: None. M. Rota: None. D. Saur: None. B. Seidler: None. I. Yoshino: None. M. Moccetti: None. T. Moccetti: None. J.M. Hare: None. M.A. Perrella: None. I.O. Rosas: None. A. Leri: Other; Significant; Member of AAL Scientifics Co. P. Anversa: Other; Significant; Member of autologous regeneration, Member AAL Scientifics.
- © 2016 by American Heart Association, Inc.