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用于人类肝功能研究及药物和候选药物肝毒性评估的新型三维培养系统的进展

Evolution of Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates.

作者信息

Andersson Tommy B

机构信息

Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.

出版信息

Basic Clin Pharmacol Toxicol. 2017 Oct;121(4):234-238. doi: 10.1111/bcpt.12804. Epub 2017 Jul 3.

Abstract

The pharmaceutical industry urgently needs reliable pre-clinical models to evaluate the efficacy and safety of new chemical entities before they enter the clinical trials. Development of in vitro model systems that emulate the functions of the human liver organ has been an elusive task. Cell lines exhibit a low drug-metabolizing capacity and primary liver cells rapidly dedifferentiate in culture, which restrict their usefulness substantially. Recently, the development of hepatocyte spheroid cultures has shown promising results. The proteome and transcriptome in the spheroids were similar to the liver tissue, and hepatotoxicity of selected substances was detected at in vivo-relevant concentrations.

摘要

制药行业迫切需要可靠的临床前模型,以便在新化学实体进入临床试验之前评估其疗效和安全性。开发能够模拟人体肝脏器官功能的体外模型系统一直是一项难以实现的任务。细胞系的药物代谢能力较低,原代肝细胞在培养中会迅速去分化,这大大限制了它们的用途。最近,肝细胞球体培养的发展已显示出有希望的结果。球体中的蛋白质组和转录组与肝组织相似,并且在体内相关浓度下检测到了所选物质的肝毒性。

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