RNA sequencing of human bronchial epithelial cell transcriptomes after repopulation and differentiation on bronchial scaffolds from COPD patients and healthy donors

Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM). To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM. The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients. Overall design: Normal bronchial epithelial (NHBE) cells were seeded on decellularized bronchial scaffolds from 3 COPD patients and 3 healthy donors. Differentiation was induced 4 days later and repopulated scaffolds were collected after 0, 7, 14, 21, 28 and 35 days of differentiation.