Mitchell Sarah M, Meldrum Kirsty, Bateman Joshua W P, Tetley Teresa D, Doak Shareen H, Clift Martin J D
In Vitro Toxicology Group, Faculty of Medicine, Health and Life Sciences, Swansea University Medical School, Swansea University, Sketty, Wales SA2 8PP UK.
Lung Cell Biology, Section of Pharmacology and Toxicology, Airways Disease, National Heart & Lung Institute, Imperial College London, London, UK.
In Vitro Model. 2024 Aug 6;3(2-3):125-137. doi: 10.1007/s44164-024-00075-2. eCollection 2024 Jun.
Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings. Here, an in vitro model of the alveolar barrier has been created in preparation for use in the quasi-air liquid interface (qALI) and (aerosol) air-liquid interface (ALI) exposures. The model consists of an alveolar type 1-like cell line (TT1), an alveolar type 2-like cell line (NCI-H441) and a model of (alveolar) macrophages (dTHP-1). The model formulates a complex, multi-cellular system, cultured at the air-liquid interface, that mimics the apical layer of the alveolar epithelial region in the human lung. Characterisation data has shown that both TT1 and NCI-H441 epithelial cells are able to be cultured together in addition to dTHP-1 cells through imaging (morphology), pro-inflammatory response and viability measurements. This dataset also demonstrates evidence of a reasonable barrier created by the cell culture in comparison to negative controls. Furthermore, it shows that while maintaining a low baseline of (pro)-inflammatory mediator expression during normal conditions, the model is highly responsive to inflammatory stimuli. This model is proposed to be suitable for use in toxicology testing of inhaled exogenous agents.
The online version contains supplementary material available at 10.1007/s44164-024-00075-2.
由于伦理团体和公众要求避免不必要动物实验的压力不断增加，对新型、反应灵敏且具有生物学相关性的体外模型的需求激增。人类肺泡上皮模型尤其令人关注，因为需要深入研究空气污染以及吸入纳米颗粒和电子烟的影响。由于在职业和环境环境中可能接触内源性物质，肺是一个至关重要的研究器官。在此，已创建了一种肺泡屏障的体外模型，准备用于准气液界面（qALI）和（气溶胶）气液界面（ALI）暴露实验。该模型由一种1型肺泡样细胞系（TT1）、一种2型肺泡样细胞系（NCI - H441）和一种（肺泡）巨噬细胞模型（dTHP - 1）组成。该模型构建了一个复杂的多细胞系统，在气液界面培养，模拟人肺中肺泡上皮区域的顶端层。表征数据表明，通过成像（形态学）、促炎反应和活力测量，TT1和NCI - H441上皮细胞以及dTHP - 1细胞能够共同培养。与阴性对照相比，该数据集还证明了细胞培养形成了合理屏障的证据。此外，它表明该模型在正常条件下维持（促）炎介质表达的低基线水平，同时对炎症刺激高度敏感。该模型被认为适用于吸入外源性物质的毒理学测试。
在线版本包含可在10.1007/s44164 - 024 - 00075 - 2获取的补充材料。
