Université de technologie de Compiègne, CNRS, Biomechanics and Bioengineering, Centre de recherche Royallieu - CS 60319, 60203 Compiègne Cedex, France.
French National Institute for Industrial Environment and Risks, INERIS, Direction milieux et impacts sur le vivant, Verneuil-en-Halatte, France.
Toxicol In Vitro. 2023 Oct;92:105641. doi: 10.1016/j.tiv.2023.105641. Epub 2023 Jul 10.
Animal models are considered prime study models for inhalation-like toxicity assessment. However, in light of animal experimentation reduction (3Rs), we developed and investigated an alternative in vitro method to study systemic-like responses to inhalation-like exposures. A coculture platform was established to emulate inter-organ crosstalks between a pulmonary barrier, which constitutes the route of entry of inhaled compounds, and the liver, which plays a major role in xenobiotic metabolism. Both compartments (Calu-3 insert and HepG2/C3A biochip) were jointly cultured in a dynamically-stimulated environment for 72 h. The present model was characterized using acetaminophen (APAP), a well-documented hepatotoxicant, to visibly assess the passage and circulation of a xenobiotic through the device. Based on viability and functionality parameters the coculture model showed that the bronchial barrier and the liver biochip can successfully be maintained viable and function in a dynamic coculture setting for 3 days. In a stress-induced environment, present results reported that the coculture model emulated active and functional in vitro crosstalk that seemingly was responsive to xenobiotic exposure doses. The hepatic and bronchial cellular responses to xenobiotic exposure were modified in the coculture setting as they displayed earlier and stronger detoxification processes, highlighting active and functional organ crosstalk between both compartments.
动物模型被认为是评估吸入类似毒性的主要研究模型。然而，鉴于动物实验的减少（3Rs），我们开发并研究了一种替代的体外方法来研究类似于吸入暴露的全身性反应。建立了共培养平台来模拟肺屏障（构成吸入化合物进入途径）和肝脏之间的器官间串扰，肝脏在异生物质代谢中起主要作用。两个隔室（Calu-3 插入物和 HepG2/C3A 生物芯片）在动态刺激环境中共同培养 72 小时。使用已被充分记录的肝毒性药物对乙酰氨基酚（APAP）对本模型进行了表征，以直观评估异生物质通过该设备的传递和循环。基于活力和功能参数，共培养模型表明，支气管屏障和肝生物芯片可以在动态共培养环境中成功地维持 3 天的活力和功能。在应激诱导的环境中，本研究结果表明，共培养模型模拟了主动和功能的体外串扰，似乎对异生物质暴露剂量有反应。在共培养环境中，异生物质暴露对肝和支气管细胞的反应发生了改变，因为它们显示出更早和更强的解毒过程，突出了两个隔室之间的主动和功能器官串扰。
