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来自人类诱导的多能干细胞的肝细胞:建立一个体外模型来评估肝毒性测试中的种群变异性

Xiugong Gao¹, Rong Li¹, Kayla Campasino¹

¹Division of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United States.

Current research in toxicology

|June 11, 2025

概括

这项研究开发了一个体外模型,使用人类诱导的多能干细胞衍生的肝细胞来评估化学变异性. 该模型显示了对肝毒剂的多样性反应,突出了个性化毒理学的潜力.

科学领域:

毒理学毒理学毒理学
干细胞生物学干细胞生物学
基因组学就是基因组学.

背景情况:

评估化学反应的个体间变异性传统上依赖于不确定性因素.
新兴的体外模型为特定化学品的人口变异提供了定量洞察力.
人类诱导多能干细胞 (iPSC) 衍生肝细胞是此类评估的有希望的工具.

研究的目的:

建立一个体外模型来评估肝毒性测试中的种群变异性.
利用来自不同种族群体的iPSC衍生的肝细胞小组来评估个人之间的差异.
研究肝功能,基因表达和对已知的肝毒剂的细胞毒性反应的变异性.

主要方法:

来自三个种族 (黑人或非洲裔美国人,拉丁裔或西班牙裔,非西班牙裔白人) 的九个人类iPSC线的衍生性肝细胞.
进行肝功能检测并分析全球和肝脏基因表达.
评估了对四种肝毒药物的细胞毒性反应:乙氨基,特洛格利塔,滴糖酸和乌斯尼克酸.

主要成果:

来自iPSC的肝细胞组显示了肝功能,基因表达和细胞毒性反应的多样性.
在对乙氨基,托格利塔,迪格利可酸和乌斯尼克酸的反应中观察到变化.
由于模型化合物和样本大小的限制,没有检测到种族特异性影响.

结论:

开发的iPSC衍生的肝细胞模型表明肝毒性在个体间的变化.
该模型对评估药物诱导的肝损伤的种群变异性显示出希望.
需要进一步研究种族特异性毒素和更大的样本大小,以探索种族特异性影响.

关键词:

民族身份民族身份肝细胞肝细胞肝细胞肝毒性肝毒性肝毒性在体外模型模型.诱导的多能干细胞干细胞.人口变异性的人口变异性.

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