三维肝细胞模型及其在化学性肝损伤评价中的应用

Three-Dimensional Hepatocellular Models and Their Application in the Hepatic Safety Evaluation of Chemicals

肝脏是机体代谢外源性化学物的主要场所,也是化学物及其代谢产物毒作用的重要靶器官。为了更加快速、准确地对化学物引起的肝损伤进行评估,选择贴近人体的细胞模型和培养方法至关重要。近年来研究发展了多种人源体外肝细胞模型,其中新兴的三维(3D)肝细胞体外模型具有类似体内肝脏表型、代谢能力,并适于长期体外培养,为药物等化学物的肝毒性测试提供了有力的体外评价工具。本文主要介绍目前常用的肝细胞模型的特点,以及球体模型、生物反应器、3D打印和肝脏芯片等3D培养系统,概述了这些模型在化学性肝损伤评估中的应用进展。

Liver is not only the main organ for the metabolism of exogenous chemical, but also an important target organ for the toxic action by chemicals and their metabolites. In order to accurately and efficiently assess the liver toxicity by chemicals, it is critical to select appropriate and fit-for-purpose in vitro models that are close to the human. In recent years, a variety of human-derived in vitro hepatocyte models have been developed. Among them, the emerging in vitro three-dimensional(3 D) hepatocyte model has similar liver phenotype and metabolic capacity in vivo, and is suitable for long-term in vitro culture, providing powerful in vitro platforms for the safety evaluation of drugs and other chemicals. This review mainly introduced the characteristics of currently commonly used hepatocyte models, as well as 3 D culture systems such as spheroid models, bioreactors, 3 D printing and liver chips, and summarized the advances in the application of these models in the evaluation of chemical liver injury.