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基于细胞的微阵列和高通量药物筛选应用的微工程方法。

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications.

机构信息

Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Biofabrication. 2011 Sep;3(3):034101. doi: 10.1088/1758-5082/3/3/034101. Epub 2011 Jul 1.

Abstract

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

摘要

从数百万种药物候选物中筛选有效的治疗药物既昂贵又耗时,并且由于广泛使用动物,常常面临问题。为了提高成本效益,并尽量减少药物研究中的动物试验,已经开发出具有多孔板测定法的体外单层细胞微阵列。将细胞微阵列与微流控系统集成,实现了自动化和受控的组件加载,显著减少了候选化合物和靶细胞的消耗。尽管与传统的体外测试系统和体内动物模型相比,这些方法大大提高了通量,但这些平台的相关成本仍然高得令人望而却步。此外,需要三维(3D)基于细胞的药物筛选模型,以模拟体内微环境和天然组织的功能。在这里,我们介绍了可以用于开发 3D 基于细胞的药物筛选测定的最新微工程方法。我们重点介绍了基于活细胞的阵列、微流控细胞培养系统的 3D 体外细胞培养系统及其在高通量药物筛选中的应用。我们得出的结论是,在新兴的微工程方法中,生物打印具有很大的潜力,可以提供具有高时间、空间控制和多功能性的可重复的 3D 基于细胞的构建体。

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