TY - JOUR KW - Chronic inflammation KW - Lab-on-a-chip KW - Respiratory Tract Diseases KW - Tissue engineering AU - Akina Mori AU - Marjolein Vermeer AU - Lenie J. van den Broek AU - Jeroen Heijmans AU - Arnaud Nicolas AU - Josse Bouwhuis AU - Todd Burton AU - Kazushi Matsumura AU - Kazuhiro Ohashi AU - Shigeaki Ito AU - Bart Kramer AB - Airway inflammation, a protective response in the human body, can disrupt normal organ function when chronic, as seen in chronic obstructive pulmonary disease (COPD) and asthma. Chronic bronchitis induces goblet cell hyperplasia and metaplasia, obstructing airflow. Traditional animal testing is often replaced by in vitro three-dimensional cultures of human epithelial cells to assess chronic cell responses. However, these cells are cultured horizontally, differing from the tubular structure of the human airway and failing to accurately reproduce airway stenosis. To address this, we developed the Bronchus-on-a-Chip (BoC) system. The BoC uses a novel microfluidic design in a standard laboratory plate, embedding 62 chips in one plate. Human bronchial epithelial cells were cultured against a collagen extracellular matrix for up to 35 days. Characterization included barrier integrity assays, microscopy, and histological examination. Cells successfully cultured in a tubular structure, with the apical side air-lifted. Epithelial cells differentiated into basal, ciliated, and secretory cells, mimicking human bronchial epithelium. Upon exposure to inducers of goblet cell hyperplasia and metaplasia, the BoC system showed mucus hyperproduction, replicating chronic epithelial responses. This BoC system enhances in vitro testing for bronchial inflammation, providing a more human-relevant and high-throughput method. BT - Scientific Reports DA - 2024-11-01 DO - 10.1038/s41598-024-77665-3 IS - 1 LA - en N2 - Airway inflammation, a protective response in the human body, can disrupt normal organ function when chronic, as seen in chronic obstructive pulmonary disease (COPD) and asthma. Chronic bronchitis induces goblet cell hyperplasia and metaplasia, obstructing airflow. Traditional animal testing is often replaced by in vitro three-dimensional cultures of human epithelial cells to assess chronic cell responses. However, these cells are cultured horizontally, differing from the tubular structure of the human airway and failing to accurately reproduce airway stenosis. To address this, we developed the Bronchus-on-a-Chip (BoC) system. The BoC uses a novel microfluidic design in a standard laboratory plate, embedding 62 chips in one plate. Human bronchial epithelial cells were cultured against a collagen extracellular matrix for up to 35 days. Characterization included barrier integrity assays, microscopy, and histological examination. Cells successfully cultured in a tubular structure, with the apical side air-lifted. Epithelial cells differentiated into basal, ciliated, and secretory cells, mimicking human bronchial epithelium. Upon exposure to inducers of goblet cell hyperplasia and metaplasia, the BoC system showed mucus hyperproduction, replicating chronic epithelial responses. This BoC system enhances in vitro testing for bronchial inflammation, providing a more human-relevant and high-throughput method. PY - 2024 EP - 26248 T2 - Scientific Reports TI - High-throughput Bronchus-on-a-Chip system for modeling the human bronchus UR - https://www.nature.com/articles/s41598-024-77665-3 VL - 14 Y2 - 2024-11-06 SN - 2045-2322 ER -