Zhejiang University, Department of Chemical and Biochemical Engineering, Zhejiang, PR China.
Expert Opin Drug Metab Toxicol. 2010 Jun;6(6):733-46. doi: 10.1517/17425251003674356.
Hepatotoxicity is the most frequent reason for the withdrawal of an approved drug from the market. Monolayer culture of hepatocyte in two-dimension, which is relatively inexpensive, convenient and easy to use, serves a traditional hepatocyte-based high-content screening for identifying hepatotoxic side effects of tested drugs. However, two-dimensional methods have their limitations in lack of insensitivity on reflection of drug hepatotoxicity. Three-dimensional (3D) cultures of hepatocytes in sandwich, spheroid and gel entrapment provide a microenvironment for high expression of liver-specific functions and are being proposed for prediction of drug hepatotoxicity.
This review addressed the reliability of 3D culture models on screening hepatotoxic drugs with particular emphasis on gel entrapment culture model due to its more systematic data on drug testing.
The reader will gain a comprehensive understanding of the improved prediction efficacy of 3D culture models.
Hepatocytes in 3D cultures, although in need of further standardization required by the throughput operation, show great potential in attempts to ensure the efficacy on prediction of drug hepatotoxicity.
肝毒性是最常见的原因之一，从市场上撤回一个批准的药物。单层培养的肝细胞在二维，这是相对便宜，方便，易于使用，作为传统的基于肝细胞的高通量筛选鉴定肝毒性的副作用的测试药物。然而，二维方法有其局限性，缺乏对药物肝毒性的敏感性。三维（3D）培养的肝细胞在三明治，球状体和凝胶包埋提供了一个微环境为高表达的肝脏特异性功能，并提出了用于预测药物肝毒性。
本文探讨了三维培养模型筛选肝毒性药物的可靠性，特别强调了由于其在药物测试方面有更系统的数据，所以凝胶包埋培养模型。
读者将全面了解三维培养模型预测效果的提高。
三维培养的肝细胞，虽然需要进一步的标准化，由吞吐量操作要求，显示出巨大的潜力，在试图确保疗效预测药物肝毒性。
