刘薇^1,,,
梅玺丽¹,
陈雨萌¹,
向哲源¹,
高泽欣¹,
邢立国²,
赵慧敏¹,
刘猛¹,
陈景文¹
1. 大连理工大学环境学院, 工业生态与环境工程重点实验室, 大连 116024;
2. 中化集团沈阳化工研究院有限公司, 沈阳 110027

作者简介: 刘薇(1980-),女,博士,教授,研究方向为持久性有机污染物毒性效应和机理以及干细胞毒理学模型原理和应用,E-mail:liu_wei@dlut.edu.cn.

通讯作者: 刘薇,liu_wei@dlut.edu.cn ;

基金项目: 国家重点研发计划项目（2018YFE0110700）；国家自然科学基金资助项目（21661142001，21777020）；中央高校基本科研业务费（DUT20LAB102，DUT20LK19）


中图分类号: X171.5

Progress in 3D Organoid Models and Application Perspectives in Toxicity Test of Chemicals

Liu Wei^1,,,
Mei Xili¹,
Chen Yumeng¹,
Xiang Zheyuan¹,
Gao Zexin¹,
Xing Liguo²,
Zhao Huimin¹,
Liu Meng¹,
Chen Jingwen¹
1. Key Laboratory of Industrial Ecology and Environmental Engineering of Ministry of Education, School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China;
2. Shenyang Research Institute of Chemical Industry of SINOCHEM Group, Shenyang 110027, China

Corresponding author: Liu Wei,liu_wei@dlut.edu.cn ;

CLC number: X171.5

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摘要:化学品毒理学评价主要采用2D细胞培养体系和动物实验模型，但2种模型均存在一定的局限性。2D细胞培养常用特定细胞系，与体内多细胞组织及其生理功能差异较大。动物实验耗时、昂贵，并受伦理学限制，且存在种属差异问题。3D类器官模型可模拟组织器官的复杂结构和功能，产生细胞间和细胞-基质相互作用，与体内生理反应更为相似，因此能更准确地反映毒性效应和机理。类器官模型在化学品毒理学评价领域具有良好的应用前景，将显著提升毒理学基础研究能力以及对化学品风险评价和管理的支撑作用，但相关研究尚处于起步阶段。本文从类器官的生理学特性、构建方法及组织类型等方面，重点讨论了类器官模型在化学品毒理学研究中的适用性，并提出了存在的挑战和对策。
关键词: 类器官/
毒理学替代法/
体外模型/
高通量测试

Abstract:Toxicity assessment of chemicals predominantly adopted either 2D cell culture or animal models whereas both models have intrinsic flaws. 2D cell culture systems are usually derived from a specific set of cell lines, differing from the tissue function encountered in vivo containing multiple cell types. Animal models are limited by the cost and time, associated ethical concerns and xenogeneity. 3D organoids achieve a greater level of structural and functional complexity more closely analogous to in vivo physiology, showing cell-cell and cell-extracellular matrix interactions, and thus enabling a more accurate reflection of the toxic effects and mechanisms. With promising perspectives, the progresses in organoid toxicology would significantly promote the fundamental toxicology research, and support the chemicals risk assessment and regulation as well. However, organoid-based toxicological research of chemicals is still in its infancy. In this review, we discussed recent developments and trends in organoid model concerning the physiological features, development systems and methods, and tissue-specific types, focusing on its feasibility in toxicological researches of chemicals, and the challenges and strategies are also proposed.
Key words:organoid/
toxicology alternatives/
in vitro model/
high-throughput test.

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