High-throughput Bronchus-on-a-Chip system for modeling the human bronchus

Scientific Reports, vol. 14, pp. 26248

Abstract

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.

Authors 9

1. A. Mori

   Japan Tobacco (Japan)

   Affiliation as printed

   Scientific Product Assessment Center, Japan Tobacco Inc, 6-2, Umegaoka, Aoba-Ku, Yokohama, Kanagawa, 227-8512, Japan

2. Marjolein Vermeer Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands

3. Lenie J. van den Broek Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands

4. Jeroen P. M. Heijmans Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands

5. Arnaud Nicolas Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands

6. Josse Bouwhuis Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands

7. Kazushi Matsumura

   Japan Tobacco (Japan)

   Affiliation as printed

   Scientific Product Assessment Center, Japan Tobacco Inc, 6-2, Umegaoka, Aoba-Ku, Yokohama, Kanagawa, 227-8512, Japan

8. Shigeaki Ito corresponding

   Japan Tobacco (Japan)

   Affiliation as printed

   Scientific Product Assessment Center, Japan Tobacco Inc, 6-2, Umegaoka, Aoba-Ku, Yokohama, Kanagawa, 227-8512, Japan. shigeaki.ito@jt.com

   Scientific Product Assessment Center, Japan Tobacco Inc, 6-2, Umegaoka, Aoba-Ku, Yokohama, Kanagawa, 227-8512, Japan

9. Bart Kramer Aachen Mimetas BV

   Mimetas (Netherlands)

   Affiliation as printed

   Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands