Jiang Yingying, Lu Lin, Du Chao, Li Yanting, Cheng Wenting, Bi Huanhuan, Li Guo, Zhuang Min, Ren Dunqiang, Wang Hongmei, Ji Xiaoya
Department of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao, China.
Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Medical College of Qingdao University, Qingdao, China.
Front Bioeng Biotechnol. 2023 Jan 6;10:1105710. doi: 10.3389/fbioe.2022.1105710. eCollection 2022.
Three-dimensional (3D) structured organoids have become increasingly promising and effective models, and there is an urgent need for reliable models to assess health effects of inhaled pollutants on the human airway. In our study, we conducted a toxicity assessment of human airway organoids (hAOs) for tire wear particles (TWPs) as an emerging inhaled pollutant. We induced primary human bronchial epithelial cells (HBECs) to generated human airway organoids, which recapitulated the key features of human airway epithelial cells including basal cells, ciliated cells, goblet cells, and club cells. TWPs generated from the wearing of tire treads were considered a major source of emerging inhaled road traffic-derived non-exhaust particles, but their health effect on the lungs is poorly understood. We used human airway organoids to assess the toxicology of tire wear particles on the human airway. In an exposure study, the inhibitory effect of TWPs on the growth of human airway organoids was observed. TWPs induced significant cell apoptosis and oxidative stress in a dose-dependent manner. From the qPCR analysis, TWPs significantly up-regulated the expression pf genes involved in the inflammation response. Additionally, the exposure of TWPs reduced gene expression associated with the function of the club cell and gene expression related to the function of basal cells. In conclusion, this was first study using human airway organoids for a toxicological assessment of TWPs, and our findings revealed that human airway organoids provide an evaluation model of inhaled pollutants potentially affecting the lungs.
三维（3D）结构化类器官已成为越来越有前景且有效的模型，并且迫切需要可靠的模型来评估吸入污染物对人体气道的健康影响。在我们的研究中，我们对作为一种新出现的吸入污染物的轮胎磨损颗粒（TWPs）进行了人体气道类器官（hAOs）的毒性评估。我们诱导原代人支气管上皮细胞（HBECs）生成人体气道类器官，其概括了人体气道上皮细胞的关键特征，包括基底细胞、纤毛细胞、杯状细胞和棒状细胞。轮胎胎面磨损产生的TWPs被认为是新出现的吸入性道路交通衍生非尾气颗粒的主要来源，但其对肺部的健康影响却知之甚少。我们使用人体气道类器官来评估轮胎磨损颗粒对人体气道的毒理学。在一项暴露研究中，观察到TWPs对人体气道类器官生长的抑制作用。TWPs以剂量依赖性方式诱导显著的细胞凋亡和氧化应激。从定量聚合酶链反应（qPCR）分析来看，TWPs显著上调了参与炎症反应的基因表达。此外，TWPs的暴露降低了与棒状细胞功能相关的基因表达以及与基底细胞功能相关的基因表达。总之，这是首次使用人体气道类器官对TWPs进行毒理学评估的研究，我们的研究结果表明人体气道类器官提供了一个评估潜在影响肺部的吸入污染物的模型。
