评估2D和3D培养肝细胞中的受体激活:对单一化合物和复杂混合物的反应
Laiba Jamshed1, Shanza Jamshed1, Richard A Frank2
1Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON L8S 4L8, Canada.
Toxics
|September 27, 2024
概括
使用McA-RH7777细胞的新3D球形模型在毒性测试中显示出更高的准确性. 这些先进的3D培养为评估对肝细胞的化学影响提供了增强的灵敏度和统一的反应.
科学领域:
- 肝细胞生物学 肝细胞生物学
- 毒理学 毒理学 毒理学
- 细胞和分子毒理学 细胞和分子毒理学
背景情况:
- 全球监管转变,比如加拿大的S-5法案 (2023年),要求朝着伦理的体外*毒性测试迈进.
- 传统的二维细胞培养不能充分模仿*in vivo*的肝脏微环境.
- 三维 (3D) 球状肝细胞培养提供了更具生理相关性的替代方案.
研究的目的:
- 开发和验证使用McA-RH7777细胞进行毒性评估的第一个3D球形模型.
- 评估模型对异生菌受体激活,细胞信号和毒性的反应.
- 为了比较3D球体与传统的2D培养的有效性,使用德克萨米他和纳夫酸微分成分 (NAFCs).
主要方法:
- 为MCA-RH7777肝细胞建立一个3D球形培养系统.
- 3D和2D培养物的暴露于德甲和NAFCs.
- 评估与异生物代谢相关的基因表达变化 (AhR,PPAR).
- 在2D和3D模型中评估细胞反应,包括细胞亡.
主要成果:
- 3D McA-RH7777球形体表现出对异生体代谢基因表达的增强敏感性和更一致的剂量反应模式.
- 在德克萨米他暴露后,在3D培养物中观察到显著的基因表达变化.
- 3D培养与2D培养相比,对NAFC诱导的亡的敏感性和耐药性呈现差异.
结论:
- 3D McA-RH7777球形模型为肝脏的毒性测试提供了更准确的肝脏微环境表示.
- 该模型增强了基因组特征的识别,并改善了对暴露在有毒物质下的细胞机制的理解.
- 优化的3D球形培养代表了伦理和有效的实验室毒理学的重大进步.
关键词:
灭症 (apoptosis) 是一种死亡的过程.细胞培养培养的细胞培养.德克萨米他是一种一个单层的单层.纳夫酸 纳夫酸 纳夫酸受体激活受体的激活方式球形状的球形状是指球形状的球形状.三维 (3D) 的三维 (3D)两个维 (2D) 的二维.更多相关视频
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