Epithelial-mesenchymal crosstalk in COPD: An update from in vitro model studies

Chronic Obstructive Pulmonary disease (COPD) involves airway inflammation and remodeling leading to small airways disease and emphysema, which results in irreversible airflow obstruction. During lung development, reciprocal interactions between the endoderm and mesoderm (epithelial-mesenchymal trophic unit (EMTU)) are essential for morphogenetic cues that direct cell proliferation, differentiation, and extracellular (ECM) production. In COPD, a significant number of the inflammation and remodeling mediators resemble those released during lung development, which has led to the hypothesis that aberrant activation of the EMTU may occur in the disease. Studies assessing lung epithelial and fibroblast function in COPD, have been primarily focused on monoculture studies. To capture the in vivo environment of the human lung and aid in the understanding of mechanisms and mediators involved in abnormal epithelial-fibroblast communication in COPD, complex co-culture models are required. In this review, we describe the studies that have used co-culture models to assess epithelial-fibroblast interactions and their role in the pathogenesis of COPD.