Abstract
Background This study is aimed at characterizing the human distal airway stem cells (DASCs) and assessing their therapeutic potential in patients with chronic, degenerative lung diseases. These findings will provide a comprehensive understanding for further clinical applications utilizing autologous airway stem cells as therapeutic intervention in respiratory diseases. Methods DASCs were isolated from healthy subjects or patients diagnosed with bronchiectasis, chronic obstructive pulmonary diseases (COPD), or interstitial lung disease (ILD). Differentiation capacity, a key property of the stem cells, was studied using a novel monolayer differentiation system. The differentiated cells were evaluated for alveolar and bronchial cell marker expression, and the quantified expression level of differentiated cells was further examined for their relationship with age and pulmonary function of the subjects. Results and Conclusions Differentiation of DASCs and tracheal stem cells (TSCs) yielded an alveolus-like structure and a tube-shaped structure, respectively, with distinct marker gene expression. Additionally, single-cell-derived clones showed diverse differentiation fates, even if the clones arise from identical or different individuals. More importantly, the alveolar differentiation potency was higher in DASCs derived from patients than from healthy people. The differentiation efficiency of DASCs also correlates with age in patients with bronchiectasis and ILD.
Highlights
In the modern world, lung disease is one of the major threats of public health worldwide, with high morbidity and mortality surpassed only by cardiovascular disease and cancer
Cell therapy using tissuespecific multipotential stem cells holds great potential as a novel strategy for lung diseases characterized by irreversible, progressive damage of airway and alveolar tissues, such as bronchiectasis, idiopathic pulmonary fibrosis (IPF), and chronic obstructive pulmonary disease (COPD)
Human airway stem cells derived from the 4th-order bronchi can be successfully cloned and propagated on a feeder culture system in vitro, expressing lung epithelial stem cell markers cytokeratin 5 (KRT5) and transformation protein 63 (P63), as well as the human-specific marker human nuclear antigen (HuNu) [10]
Summary
Lung disease is one of the major threats of public health worldwide, with high morbidity and mortality surpassed only by cardiovascular disease and cancer. Previous researches conducted by our group and others have identified local populations of adult lung stem/ progenitor cells in airway and alveolar tissues that respond to injury and airway epithelia regeneration [8,9,10,11,12,13,14,15]. They are capable of undergoing long-term self-renewal and give rise to multiple differentiated cell types. This study is aimed at characterizing the human distal airway stem cells (DASCs) and assessing their therapeutic potential in patients with chronic, degenerative lung diseases. The differentiation efficiency of DASCs correlates with age in patients with bronchiectasis and ILD
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