Scientific Product Assessment Center, Japan Tobacco Inc, 6-2, Umegaoka, Aoba-Ku, Yokohama, Kanagawa, 227-8512, Japan.
Mimetas BV, De Limes 7 2342DH, Oegstgeest, The Netherlands.
Sci Rep. 2024 Nov 1;14(1):26248. doi: 10.1038/s41598-024-77665-3.
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.
气道炎症是人体的一种保护性反应，但在慢性情况下，如慢性阻塞性肺疾病（COPD）和哮喘中，会破坏正常器官功能。慢性支气管炎会诱导杯状细胞增生和化生，从而阻塞气流。传统的动物试验通常被体外三维培养的人上皮细胞所替代，以评估慢性细胞反应。然而，这些细胞是水平培养的，与人类气道的管状结构不同，无法准确再现气道狭窄。为了解决这个问题，我们开发了支气管芯片（BoC）系统。BoC 在标准实验室板中使用新颖的微流控设计，在一个板中嵌入 62 个芯片。人类支气管上皮细胞在胶原蛋白细胞外基质上培养长达 35 天。表征包括屏障完整性测定、显微镜检查和组织学检查。细胞成功地在管状结构中培养，顶侧被空气托起。上皮细胞分化为基底细胞、纤毛细胞和分泌细胞，模拟人支气管上皮。在暴露于诱导杯状细胞增生和化生的诱导剂后，BoC 系统显示出粘液过度产生，复制了慢性上皮反应。这种 BoC 系统增强了支气管炎症的体外测试，提供了更具人类相关性和高通量的方法。
