Three-dimensional in vitro cell culture devices using patient-derived cells for high-throughput screening of drug combinations

Seok-Joon Kwon, Dongwoo Lee, Sneha Gopal, Ashlyn Ku, Hosang Moon, Jonathan S. Dordick
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引用次数: 4

Abstract

Drug discovery using traditional animal models is often inefficient because test animal models cannot accurately represent human responses, particularly in terms of toxicology and pathophysiology. For these reasons, there is an urgent need to develop in vitro human disease models to accelerate new drug development. This is especially the case for precision medicine, where current in vitro and ex vivo models are not sufficient to predict individual drug efficacy and safety across the enormous heterogeneity of populations and individuals. In addition, model cell lines cultured under non-physiological conditions do not recapitulate the complex microenvironment of patient tissues. Precision medicine using patient-derived cells and drug combination therapies may be a promising solution to overcome these limitations. Three-dimensional (3D) cell culture models can simultaneously simulate complex in vivo tissue microenvironments and be miniaturized for large-scale screening of drug combinations using limited available patient-derived cells. Recently, microfluidic and microarray platforms have been developed to mimic multiple human organs and human-specific disease states, and are becoming more commonly used in high-throughput drug screening. Herein, we highlight the current status of microfluidic-based 3D cell culture devices, such as organ/body-on-chip systems, as well as microarray-based 3D cell culture platforms, which can be combined with patient-derived cells. Miniaturized cell culture systems using patient-derived cells represent promising tools for identifying new drug combinations and also biological mechanisms that underlie drug synergies.

Abstract Image

三维体外细胞培养装置使用病人来源的细胞高通量筛选药物组合
使用传统动物模型的药物发现通常效率低下,因为实验动物模型不能准确地代表人类的反应,特别是在毒理学和病理生理学方面。由于这些原因,迫切需要开发体外人类疾病模型来加速新药的开发。对于精准医疗来说尤其如此,目前的体外和离体模型还不足以预测个体药物在巨大异质性人群和个体中的疗效和安全性。此外,在非生理条件下培养的模型细胞系不能再现患者组织的复杂微环境。使用患者来源的细胞和药物联合疗法的精准医疗可能是克服这些限制的一个有希望的解决方案。三维(3D)细胞培养模型可以同时模拟复杂的体内组织微环境,并且可以小型化,用于使用有限的患者来源细胞进行药物组合的大规模筛选。最近,微流控和微阵列平台已经发展到模拟多种人体器官和人类特异性疾病状态,并越来越多地用于高通量药物筛选。在此,我们重点介绍了基于微流体的3D细胞培养设备的现状,例如器官/人体芯片系统,以及基于微阵列的3D细胞培养平台,它们可以与患者来源的细胞相结合。使用患者来源细胞的小型化细胞培养系统是识别新药物组合和药物协同作用基础的生物学机制的有前途的工具。
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