基于人胚胎干细胞的药物毒性测试替代法研究进展  

Progress in alternative testing strategies for human embryonic stem cell-based drug toxicity

作　　者：贾栗[1] 彭辉[1] 赵增明[1] 乌瀚宝栎尔 彭双清[1] 

机构地区：[1]军事医学科学院疾病预防控制所毒理学评价研究中心,北京100071

出　　处：《中国药理学与毒理学杂志》2016年第2期173-177,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家国际科技合作专项项目(2011DFA32190)~~

摘　　要：传统的药物研发及安全性评价对实验动物的需求量大,费用高,周期长,种属差异性问题难以克服。人胚胎干细胞(h ESC)可自我更新及定向分化为多种类型的细胞,逐渐成为毒性测试体外替代法的新工具。h ESC的体外替代模型预测受试物对人体各种靶器官的毒性及毒作用机制,如生殖毒性测试模型、神经发育毒性测试模型及体外代谢模型等,结合基因组学、蛋白质组学和代谢组学等组学技术快速高效地分析多条代谢通路,寻找潜在的毒性生物标志物。在药物毒理学研究中具有广泛的应用前景。Traditional drug development and pre-clinical tests are based on animals and involve large numbers of animals, costs and long periods. Meanwhile, inter-species differences are difficult to overcome. Human embryonic stem cells （hESCs）, which can self-renew and directly differentiate to types of cells, have become a new tool for toxicity alternative testing, hESC-Based alternative testing models, such as the reproductive toxicity test system, neuro development toxicity test system and metabolic model, can be used to predict target organ toxicity and toxic mechanisms of chemicals, analyze metabolic pathways and to search for potential toxicity biomarkers, when combined with omics such techiniques as metabonomics, proteomics and genomics. Therefore, hESC-based alternative testing models have extensive application to toxicology.

关 键 词：胚胎干细胞 毒性试验 生殖毒性 神经毒性 模型 代谢 

分 类 号：R96[医药卫生—药理学]