A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications.
A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications.
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DOI：
10.1039/c6lc01422d
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发表时间：
2017-01-31
期刊：
影响因子：
6.1
通讯作者：
Hughes CCW
中科院分区：
文献类型：
--
作者：
Phan DTT;Wang X;Craver BM;Sobrino A;Zhao D;Chen JC;Lee LYN;George SC;Lee AP;Hughes CCW
越来越多的人意识到，复杂的三维（3D）器官不能很好地用单细胞类型的单层来表示-这是许多药物筛选的标准格式。为了解决这一缺陷，并以改善筛选的目标，使具有良好的疗效和低毒性的药物可以被识别，微生理系统（MPS）正在开发，更好地捕捉体内生理学的复杂性。我们之前已经描述了一种芯片上器官平台，其包含灌注的微血管，使得周围组织的存活完全取决于通过血管递送营养物。在这里，我们描述了一个阵列版本的平台，在96孔板上包含多个血管化微器官（VMO）。每个VMO都是独立可寻址的，并且通过微器官的流动由静水压力驱动。该平台易于使用，不需要外部泵或阀门，并且具有高度可重复性。作为概念验证，我们创建了阵列血管化微肿瘤（VMT），并在盲法筛选中使用这些微肿瘤来分析一个小型化合物库，包括FDA批准的抗癌药物，并成功鉴定了抗血管生成和抗肿瘤药物。该3D平台适用于在比以前更生理化的环境中对多种组织进行疗效/毒性筛选。
There is a growing awareness that complex 3-dimensional (3D) organs are not well represented by monolayers of a single cell type – the standard format for many drug screens. To address this deficiency, and with the goal of improving screens so that drugs with good efficacy and low toxicity can be identified, microphysiological systems (MPS) are being developed that better capture the complexity of in vivo physiology. We have previously described an organ-on-a-chip platform that incorporates perfused microvessels, such that survival of the surrounding tissue is entirely dependent on delivery of nutrients through the vessels. Here we describe an arrayed version of the platform that incorporates multiple Vascularized Micro-Organs (VMOs) on a 96-well plate. Each VMO is independently-addressable and flow through the micro-organ is driven by hydrostatic pressure. The platform is easy to use, requires no external pumps or valves, and is highly reproducible. As a proof-of-concept we have created arrayed Vascularized Micro Tumors (VMTs) and used these in a blinded screen to assay a small library of compounds, including FDA-approved anti-cancer drugs, and successfully identified both anti-angiogenic and anti-tumor drugs. This 3D platform is suitable for efficacy/toxicity screening against multiple tissues in a more physiological environment than previously possible.
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影响因子：
6.1
作者：
Wang X;Phan DTT;Zhao D;George SC;Hughes CCW;Lee AP
通讯作者：
Lee AP
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
4.6
作者：
Mathur A;Loskill P;Shao K;Huebsch N;Hong S;Marcus SG;Marks N;Mandegar M;Conklin BR;Lee LP;Healy KE
通讯作者：
Healy KE
影响因子：
3.2
作者：
Brown, Jacquelyn A.;Pensabene, Virginia;Wikswo, John P.
通讯作者：
Wikswo, John P.
DOI：
10.1126/science.1188302
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huh D;Matthews BD;Mammoto A;Montoya-Zavala M;Hsin HY;Ingber DE
通讯作者：
Ingber DE