Smoking Impairs the Immunomodulatory Capacity of Lung Resident Mesenchymal Stem Cells in COPD.

Tobacco smoking is the main environmental risk factor of Chronic Obstructive Pulmonary Disease (COPD), but not all smokers develop the disease. A population of lung resident mesenchymal stem cells (LR-MSC) exist in healthy lungs, but how tobacco smoking affects them and their role in COPD have not been assessed yet. Using a sphere based culture technique, LR-MSC were isolated from lung tissue obtained from non-smokers, current and former smokers with and without COPD (n=53). Cells were characterized by flow cytometry and affymetrix arrays. Their immunomodulatory capacity was assessed in vitro using co-cultures with T cells, after pre-incubation with 2.5% and 5% of cigarette smoke extracts (CSE). We were able to isolate LR-MSC expressing similar phenotypic markers in all study groups. LR-MSCs from current smokers with COPD expressed different levels of CX3CL1 and CCL5 cytokines and were unable to modulate CD8+ T cells proliferation. Pre-incubation of LR-MSCs with CSE reduced their immunomodulatory capacity. In conclusion: (1) LR-MSC can be isolated in similar amounts from never smokers and smokers with and without COPD; (2) their immunomodulatory capacity is impaired in current smokers with COPD but not in those with normal lung function; and, (3) this is reversible after quitting and reproducible in vitro.