基于人脑类器官模型的神经毒性研究进展  

Advances in neurotoxicity research based on brain organoids

作　　者：王志秋 张晋 石洪達 黄琰 岑小波[2] 卜迁 WANG Zhi-qiu;ZHANG Jin;SHI Hong-da;HUANG Yan;CEN Xiao-bo;BU Qian(Department of Health Toxicology and Pathology,West China School of Public Health,Sichuan University/West China Fourth Hospital,Chengdu,Sichuan 610041,China;不详)

机构地区：[1]四川大学华西公共卫生学院/华西第四医院卫生毒理与病理学系,四川成都610041 [2]四川大学华西医院国家成都新药安全性评价中心,四川成都610041

出　　处：《现代预防医学》2023年第23期4404-4411,共8页Modern Preventive Medicine

基　　金：四川省卫生健康委医学科技项目(21PJ064);成都市科技局技术创新研发项目(2022-YF05-01496-SN)。

摘　　要：大脑是人体毒性效应最敏感的器官之一,化学物引起的神经毒性可造成神经系统的永久性损伤,然而大多化学物的神经毒性因缺乏高仿真的复杂模型而未得到充分评估。脑类器官是由人多能干细胞分化而来的3D细胞模型,包含了十余种神经细胞类型,能够模拟胚胎发育过程中人脑特有的结构和神经生理特性。相较于传统2D神经细胞和实验动物模型,脑类器官能够更好地模拟人类大脑特征,在化学物神经毒性评估方面具有独特优势。近年来,脑类器官模型被应用于药物、食源性物质、成瘾性物质、新污染物、有害金属、纳米材料等多种化学物的神经毒性研究,是评估化学物神经毒性及深入研究毒性机制的理想模型。本文系统总结了脑类器官模型在药物、有机化学物、无机化学物神经毒性方面的应用及研究进展,并探讨了目前脑类器官模型的局限性,展望了未来脑类器官模型在神经毒性研究中的前景。The brain is one of the most sensitive organs to toxic effects.Neurotoxicity induced by chemicals can cause permanent damage to the nervous system,yet the neurotoxicity of most chemicals has not been adequately assessed due to the lack of highly simulated complex models.Brain organoids,self-organizing 3D models derived from human pluripotent stem cells,contain more than ten types of neural cells and can simulate the unique structural and neurophysiological properties of the human brain during embryonic development.Compared with traditional 2D neural cells and experimental animal models,brain organoids can better simulate the characteristics of the human brain and have unique advantages of assessing human neurotoxicity.In recent years,brain organoids have been applied to neurotoxicity studies of various chemicals such as drugs,food-borne chemicals,addictive substances,new pollutants,harmful metals,and nanomaterials.Accordingly,brain organoids are ideal models for assessing neurotoxicity and studying further toxicity mechanisms.In this article,we systematically summarize the applications and research progress of brain organoids in the neurotoxicity of drugs,organic chemicals,and inorganic chemicals.Finally,we discuss the current limitations of brain organoids,and look forward to the prospects of brain organoids in neurotoxicity research.

关 键 词：人多能干细胞 脑类器官 神经毒性 安全性评价 

分 类 号：R994[医药卫生—毒理学]