Phan Duc T T, Wang Xiaolin, Craver Brianna M, Sobrino Agua, Zhao Da, Chen Jerry C, Lee Lilian Y N, George Steven C, Lee Abraham P, Hughes Christopher C W
Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.
Department of Micro/Nano Electronics, Shanghai Jiao Tong University, Shanghai, 200240, China.
Lab Chip. 2017 Jan 31;17(3):511-520. doi: 10.1039/c6lc01422d.
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.
人们越来越意识到，复杂的三维（3D）器官无法通过单一细胞类型的单层细胞很好地呈现出来，而单层细胞是许多药物筛选的标准形式。为了解决这一缺陷，并为了改进筛选方法以便能够识别出疗效好且毒性低的药物，正在开发微生理系统（MPS），其能更好地捕捉体内生理学的复杂性。我们之前描述过一种芯片上器官平台，该平台整合了灌注微血管，使得周围组织的存活完全依赖于通过血管输送营养物质。在此，我们描述该平台的阵列版本，其在96孔板上整合了多个血管化微器官（VMO）。每个VMO都是独立可控的，并且通过微器官的流动由静水压力驱动。该平台易于使用，无需外部泵或阀门，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检测一小批化合物库，包括美国食品药品监督管理局（FDA）批准的抗癌药物，并成功识别出抗血管生成和抗肿瘤药物。这个3D平台适用于在比以往更接近生理环境的条件下针对多种组织进行疗效/毒性筛选。
