Pu Yong, Gingrich Jeremy, Veiga-Lopez Almudena
Department of Pathology, University of Illinois at Chicago, 909 S. Wolcott Ave, Rm 6093, Chicago, IL 60612, USA.
Department of Pharmacology and Toxicology, Michigan State University, USA.
Lab Chip. 2021 Feb 9;21(3):546-557. doi: 10.1039/d0lc01013h.
Placental trophoblast cells invasion into the maternal uterus is an essential and complex event in the formation of the maternal-fetal interface. Commonly used two-dimensional (2D) cell invasion tools do not accurately represent the in vivo cell invasion microenvironment. Three-dimensional (3D) silicone polymer polydimethylsiloxane (PDMS) microfluidic platforms are an emerging technology in developing organ-on-a-chip models. Here, we present a placenta-on-a-chip platform that enables the evaluation of trophoblast invasion with intraluminal flow within an engineered PDMS 3D microfluidic chip. This platform reproduces key elements of the placental microenvironment, including endothelial and trophoblast cells, layered with an extracellular matrix, and incorporates dynamic medium flow while allowing for real-time monitoring, imaging, evaluation of trophoblast cell invasion, and heterocellular cell-to-cell interactions. Coupled with fluorescent cell tagging and flow cytometry, this platform also allows collection of the invasive cells. This will help our understanding of pathways that regulate trophoblast cell invasion and may prove important for toxicological screening of exposures that interfere with invasiveness in a complex organ such as the placenta.
胎盘滋养层细胞侵入母体子宫是母胎界面形成过程中一个必不可少且复杂的事件。常用的二维（2D）细胞侵袭工具无法准确呈现体内细胞侵袭的微环境。三维（3D）硅聚合物聚二甲基硅氧烷（PDMS）微流控平台是开发芯片器官模型的一项新兴技术。在此，我们展示了一种芯片胎盘平台，该平台能够在工程化的PDMS 3D微流控芯片内通过管腔内流动来评估滋养层细胞的侵袭。这个平台再现了胎盘微环境的关键要素，包括内皮细胞和滋养层细胞，与细胞外基质分层，并结合动态培养基流动，同时允许对滋养层细胞侵袭以及异体细胞间相互作用进行实时监测、成像和评估。结合荧光细胞标记和流式细胞术，该平台还能收集侵袭细胞。这将有助于我们理解调节滋养层细胞侵袭的途径，并且可能对干扰胎盘等复杂器官侵袭性的暴露进行毒理学筛选具有重要意义。
