A novel method for expansion and differentiation of mouse tracheal epithelial cells in culture

Air-liquid interface (ALI) cultures of mouse tracheal epithelial cells (MTEC) are a well-established model to study airway epithelial cells, but current methods require large numbers of animals which is unwanted in view of the 3R principle and introduces variation. Moreover, stringent breeding schemes are frequently needed to generate sufficient numbers of genetically modified animals. Current protocols do not incorporate expansion of MTEC, and therefore we developed a protocol to expand MTEC while maintaining their differentiation capacity. MTEC were isolated and expanded using the ROCK inhibitor Y-27632 in presence or absence of the γ-secretase inhibitor DAPT, a Notch pathway inhibitor. Whereas MTEC proliferated without DAPT, growth rate and cell morphology improved in presence of DAPT. ALI-induced differentiation of expanded MTEC resulted in an altered capacity of basal cells to differentiate into ciliated cells, whereas IL-13-induced goblet cell differentiation remained unaffecte

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis

The hallmark features of COPD (inflammation, fibrosis, and mucus hypersecretion) are driven by distinct pathogenic progenitors which pre-exist as minor populations in healthy lungs but dominate in the disease state relative to normal lung stem cells. © 2020 Elsevier Inc.Chronic obstructive pulmonary disease (COPD) is a progressive condition of chronic bronchitis, small airway obstruction, and emphysema that represents a leading cause of death worldwide. While inflammation, fibrosis, mucus hypersecretion, and metaplastic epithelial lesions are hallmarks of this disease, their origins and dependent relationships remain unclear. Here we apply single-cell cloning technologies to lung tissue of patients with and without COPD. Unlike control lungs, which were dominated by normal distal airway progenitor cells, COPD lungs were inundated by three variant progenitors epigenetically committed to distinct metaplastic lesions. When transplanted to immunodeficient mice, these variant clones induced pathology akin to the mucous and squamous metaplasia, neutrophilic inflammation, and fibrosis seen in COPD. Remarkably, similar variants pre-exist as minor constituents of control and fetal lung and conceivably act in normal processes of immune surveillance. However, these same variants likely catalyze the pathologic and progressive features of COPD when expanded to high numbers

Airway epithelial cell cultures for studying obstructive lung disease effects of IL-13 and cigarette smoke

The studies presented in this thesis were aimed at developing and using in vitro models that could benefit research towards understanding asthma and COPD. We used an in vitro model representing a Th2-high gene signature and studied how this gene signature may be affected by external factors such as cigarette smoke or drugs. Using these in vitro models may help to predict clinical outcomes, although they will require extensive validation. We also investigated the possibility of using primary human airway epithelial cells to model bacterial and viral exacerbations. Whereas this model is currently still under investigation, it could be particularly useful to study possible biomarkers of exacerbations and how these may be affected by external factors. Additionally, we also developed a new method to expand and differentiate mouse tracheal epithelial cells in vitro. Overall, studying airway epithelial cells may provide important clues for understanding disease pathogenesis, lead to identification of new treatment targets, and may provide important biomarkers. Using airway epithelial cells and their derived biomarkers could significantly improve our understanding in disease phenotypes of asthma and COPD. Additionally, with increasing knowledge of the disease phenotypes, we could better address the unmet need in treatment of asthma and COPD. LUMC / Geneeskund

Airway epithelial cell cultures for studying obstructive lung disease effects of IL-13 and cigarette smoke

The studies presented in this thesis were aimed at developing and using in vitro models that could benefit research towards understanding asthma and COPD. We used an in vitro model representing a Th2-high gene signature and studied how this gene signature may be affected by external factors such as cigarette smoke or drugs. Using these in vitro models may help to predict clinical outcomes, although they will require extensive validation. We also investigated the possibility of using primary human airway epithelial cells to model bacterial and viral exacerbations. Whereas this model is currently still under investigation, it could be particularly useful to study possible biomarkers of exacerbations and how these may be affected by external factors. Additionally, we also developed a new method to expand and differentiate mouse tracheal epithelial cells in vitro. Overall, studying airway epithelial cells may provide important clues for understanding disease pathogenesis, lead to identification of new treatment targets, and may provide important biomarkers. Using airway epithelial cells and their derived biomarkers could significantly improve our understanding in disease phenotypes of asthma and COPD. Additionally, with increasing knowledge of the disease phenotypes, we could better address the unmet need in treatment of asthma and COPD. </div

Airway epithelial cell cultures for studying obstructive lung disease effects of IL-13 and cigarette smoke

The studies presented in this thesis were aimed at developing and using in vitro models that could benefit research towards understanding asthma and COPD. We used an in vitro model representing a Th2-high gene signature and studied how this gene signature may be affected by external factors such as cigarette smoke or drugs. Using these in vitro models may help to predict clinical outcomes, although they will require extensive validation. We also investigated the possibility of using primary human airway epithelial cells to model bacterial and viral exacerbations. Whereas this model is currently still under investigation, it could be particularly useful to study possible biomarkers of exacerbations and how these may be affected by external factors. Additionally, we also developed a new method to expand and differentiate mouse tracheal epithelial cells in vitro. Overall, studying airway epithelial cells may provide important clues for understanding disease pathogenesis, lead to identification of new treatment targets, and may provide important biomarkers. Using airway epithelial cells and their derived biomarkers could significantly improve our understanding in disease phenotypes of asthma and COPD. Additionally, with increasing knowledge of the disease phenotypes, we could better address the unmet need in treatment of asthma and COPD. </div

Azithromycin differentially affects the IL-13-induced expression profile in human bronchial epithelial cells

Pathogenesis and treatment of chronic pulmonary disease

Use of airway epithelial cell culture to unravel the pathogenesis and study treatment in obstructive airway diseases

Pathogenesis and treatment of chronic pulmonary disease

Therapeutic Application of an Extract of Helicobacter pylori Ameliorates the Development of Allergic Airway Disease

Host-parasite interactio