Kulthong Kornphimol, Duivenvoorde Loes, Mizera Barbara Z, Rijkers Deborah, Dam Guillaume Ten, Oegema Gerlof, Puzyn Tomasz, Bouwmeester Hans, van der Zande Meike
Division of Toxicology, Wageningen University P.O. Box 8000, 6700 EA, Wageningen The Netherlands.
RIKILT-Wageningen Research P.O. Box 230, 6700 AE, Wageningen The Netherlands
RSC Adv. 2018 Sep 19;8(57):32440-32453. doi: 10.1039/c8ra05430d. eCollection 2018 Sep 18.
Novel microfluidic technologies allow the manufacture of organ-on-a-chip systems that hold great promise to adequately recapitulate the biophysical and functional complexity of organs found . In this study, a gut-on-a-chip model was developed aiming to study the potential cellular association and transport of food contaminants. Intestinal epithelial cells (Caco-2) were cultured on a porous polyester membrane that was tightly clamped between two glass slides to form two separate flow chambers. Glass syringes, polytetrafluoroethylene tubing and glass microfluidic chips were selected to minimize surface adsorption of the studied compounds ( highly lipophilic dioxins), during the transport studies. Confocal microscopy studies revealed that, upon culturing under constant flow for 7 days, Caco-2 cells formed complete and polarized monolayers as observed after culturing for 21 days under static conditions in Transwells. We exposed Caco-2 monolayers in the chip and Transwell to a mixture of 17 dioxin congeners (7 polychlorinated dibenzo--dioxins and 10 polychlorinated dibenzofurans) for 24 h. Gas chromatography-high resolution mass spectrometry was used to assess the cellular association and transport of individual dioxin congeners across the Caco-2 cell monolayers. After 24 h, the amount of transported dioxin mixture was similar in both the dynamic gut-on-a-chip model and the static Transwell model. The transport of individual congeners corresponded with their number of chlorine atoms and substitution patterns as revealed by quantitative structure-property relationship modelling. These results show that the gut-on-a-chip model can be used, as well as the traditional static Transwell system, to study the cellular association and transport of lipophilic compounds like dioxins.
新型微流控技术能够制造出具有巨大潜力的芯片器官系统，有望充分再现所发现器官的生物物理和功能复杂性。在本研究中，开发了一种肠道芯片模型，旨在研究食物污染物的潜在细胞关联和转运。将肠道上皮细胞（Caco-2）培养在多孔聚酯膜上，该膜被紧紧夹在两个载玻片之间，形成两个独立的流动腔室。在转运研究过程中，选择玻璃注射器、聚四氟乙烯管和玻璃微流控芯片，以尽量减少所研究化合物（高亲脂性二噁英）的表面吸附。共聚焦显微镜研究表明，在恒定流动条件下培养7天后，Caco-2细胞形成了完整且极化的单层，这与在Transwell中静态条件下培养21天后观察到的情况相同。我们将芯片和Transwell中的Caco-2单层暴露于17种二噁英同系物（7种多氯代二苯并 - 对 - 二噁英和10种多氯代二苯并呋喃）的混合物中24小时。使用气相色谱 - 高分辨率质谱法评估单个二噁英同系物穿过Caco-2细胞单层的细胞关联和转运情况。24小时后，动态肠道芯片模型和静态Transwell模型中转运的二噁英混合物量相似。定量结构 - 性质关系建模显示，单个同系物的转运与其氯原子数量和取代模式相对应。这些结果表明，肠道芯片模型以及传统的静态Transwell系统都可用于研究二噁英等亲脂性化合物的细胞关联和转运。
