CEC01-03 The current biological understanding of the respiratory tract, the in vitro models available as well as their use

Abstract

The main function of the human airway epithelium is to generate sterile atmosphere in the alveolar region where the gas exchange occurs. As the first line of defence against airborne pathogens, the airway epithelium acts as key barrier through mucociliary clearance and innate immune defence mechanisms. Airway epithelium is also an important immuno-regulator through production of key messengers and physical interactions with immune cells. Upon activation, respiratory epithelial cells react by producing pro-inflammatory cytokines, chemokines and metalloproteinases to recruit and activate immune cells such as neutrophils, basophils, or to initiate the adaptive immunity via dendritic cells. Interest in the use of 3D reconstituted human in vitro tissues (ALI cultures) is increasing in recent years for the study of respiratory diseases such as Asthma, Chronic Obstructive Pulmonary Disease (COPD), Bacterial and viral infections, etc.

Genetic and epigenetic diversity in ALIs with single donors allow stratification and patient specific profiling in toxicology and drug testing. On the other hand, ALIs generated with a mixture of cells from several individuals give a snapshot of global reaction of a small population when exposed to a chemical compound.

This talk will describe the in vitro upper and lower respiratory tract models currently available to simulate the structure and function of human lung epithelial tissues, such as organoids, lung-on-a-chip, transwell inserts ALI cultures. The use of these models for diverse applications will also be discussed, including the evaluation of the barrier function, local tolerance, airway inflammation, sensitization, as well as the respiratory diseases (lung fibrosis, cancers), etc.