人诱导多能干细胞在药物早期毒性评价中的应用

发布时间：2018-05-08 14:21

本文选题：诱导多能干细胞 + 药物评价　；参考：《中国药理学与毒理学杂志》2015年04期

【摘要】：人诱导多能干细胞与人胚胎干细胞相似,在体外可分化为各种类型的体细胞,其来源充足,可针对个人或某种疾病取材,为药物早期毒性评价体外替代方法提供了一个新的可选细胞模型。目前,利用人诱导多能干细胞获得的心肌细胞用于药物引起的心率改变、QT间期延长和心肌损伤等心脏毒性评价;利用其获得的神经细胞,结合高通量、高内涵技术及电生理学技术,可用于药物引起的神经突出生长异常、电生理改变及神经发育毒性评价;利用人诱导多能干细胞可获得个体特异性的大量肝细胞,具有较高的细胞色素P450酶活性,能够比较真实的反映人肝细胞的代谢特征,用于评价药物肝细胞毒性;人诱导多能干细胞具有多能性,在体外可分化为外、中和内胚层,具有用于发育毒性评价的可能性,对三胚层相应标志分子的检测有助于发育毒性评价终点的确立;人诱导多能干细胞还可用作3D培养的种子细胞,构建三维立体组织和器官模型,用于药物早期毒性评价,进一步缩小细胞水平与体内水平评价结果的差异。
[Abstract]:Human induced pluripotent stem cells, similar to human embryonic stem cells, can differentiate into various types of somatic cells in vitro, from sufficient sources to be drawn from individuals or from a disease, It provides a new alternative cell model for early toxicity evaluation of drugs in vitro. At present, cardiomyocytes obtained from human induced pluripotent stem cells are used to evaluate cardiac toxicity, such as prolongation of QT interval and myocardial injury induced by drugs, and use of the acquired nerve cells to combine with high throughput. High-intension technique and electrophysiological technique can be used to evaluate the nerve protrusion growth abnormality, electrophysiological changes and neurodevelopmental toxicity caused by drugs, and a large number of individual specific hepatocytes can be obtained by using human induced pluripotent stem cells. It has high cytochrome P450 enzyme activity, which can truly reflect the metabolic characteristics of human hepatocytes, and can be used to evaluate the hepatocyte toxicity of drugs, and human induced pluripotent stem cells are pluripotent and can differentiate into outer, neutral endoderm in vitro. Potential for developmental toxicity assessment, the detection of corresponding marker molecules in the tridermal layer contributes to the establishment of developmental toxicity assessment endpoints, and human induced pluripotent stem cells can also be used as seed cells in 3D culture, Three-dimensional tissue and organ models were constructed to evaluate the early toxicity of drugs and to further reduce the difference between cellular and in-vivo evaluation results.
【作者单位】：军事医学科学院疾病预防控制研究所毒理学评价研究中心;
【基金】：国家自然科学基金青年基金(81202603) 科技部国际合作项目(2011DFA32190)~~
【分类号】：R96

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