Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics.
Image-Assisted Microvessel-on-a-Chip Platform for Studying Cancer Cell Transendothelial Migration Dynamics.
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DOI：
10.1038/s41598-018-30776-0
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发表时间：
2018-08-20
影响因子：
4.6
通讯作者：
Huang YYS
中科院分区：
文献类型：
--
作者：
Bertulli C;Gerigk M;Piano N;Liu Y;Zhang D;Müller T;Knowles TJ;Huang YYS
随着减少体内方法的推动，对在体外重现体内设置的微生理学模型的需求急剧增加。在这里，我们提出了一种细胞外基质集成微流控芯片，其具有直径约100 µm的圆形微血管。我们的系统显示了广泛的用户适应的有利特征：简化的血管创建程序，最大限度地减少试剂和细胞的使用，以及将活细胞成像和图像分析结合起来以研究3D中细胞-微环境相互作用的动力学的能力。使用该平台，跟踪单个乳腺癌细胞（LM 2 -4175）离开血管腔进入周围细胞外基质的动态过程。在这里，我们表明，内皮衬里的存在显着减少了癌症退出事件超过15小时的成像时间：要么没有癌细胞退出，或自发退出的分数与接近内皮屏障的癌细胞数量呈正相关。在3D血管腔内绘制单个癌细胞的z位置的能力使我们能够动态观察癌细胞的迁移“热点”。我们还认为微血管质量的变化可能导致两种不同类型的癌症迁移行为。我们的研究结果提供了一个易处理的体外模型，适用于微血管研究的其他领域。
With the push to reduce in vivo approaches, the demand for microphysiological models that recapitulate the in vivo settings in vitro is dramatically increasing. Here, we present an extracellular matrix-integrated microfluidic chip with a rounded microvessel of ~100 µm in diameter. Our system displays favorable characteristics for broad user adaptation: simplified procedure for vessel creation, minimised use of reagents and cells, and the ability to couple live-cell imaging and image analysis to study dynamics of cell-microenvironment interactions in 3D. Using this platform, the dynamic process of single breast cancer cells (LM2-4175) exiting the vessel lumen into the surrounding extracellular matrix was tracked. Here, we show that the presence of endothelial lining significantly reduced the cancer exit events over the 15-hour imaging period: there were either no cancer cells exiting, or the fraction of spontaneous exits was positively correlated with the number of cancer cells in proximity to the endothelial barrier. The capability to map the z-position of individual cancer cells within a 3D vessel lumen enabled us to observe cancer cell transmigration ‘hot spot’ dynamically. We also suggest the variations in the microvessel qualities may lead to the two distinct types of cancer transmigration behaviour. Our findings provide a tractable in vitro model applicable to other areas of microvascular research.
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影响因子：
19
作者：
Huh, Dongeun;Hamilton, Geraldine A.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
9.8
作者：
Bouis, Diane;Hospers, Geke A. P.;Mulder, Nanno H.
通讯作者：
Mulder, Nanno H.
影响因子：
3.7
作者：
Farahat, Waleed A.;Wood, Levi B.;Asada, H. Harry
通讯作者：
Asada, H. Harry
影响因子：
4.1
作者：
Esch, Mandy B.;Post, David J.;Stokol, Tracy
通讯作者：
Stokol, Tracy
影响因子：
6.1
作者：
Bogorad, Max I.;DeStefano, Jackson;Karlsson, Johan;Wong, Andrew D.;Gerecht, Sharon;Searson, Peter C.
通讯作者：
Searson, Peter C.