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相关概念视频

Toxicity Testing in Animals01:23

Toxicity Testing in Animals

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

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Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
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用临床和临床前仪器仪表进行毒性评估的体外人肝模型.

Eneko Madorran1, Lidija Kocbek Šaherl1, Mateja Rakuša1

  • 1Faculty of Medicine, Institute of Anatomy, Histology and Embryology, University of Maribor, Taborska Ulica 8, 2000 Maribor, Slovenia.

Pharmaceutics
|May 25, 2024
PubMed
概括

研究人员开发了一种新的体外肝脏模型,使用模仿人类肝脏微环境的初级肝细胞. 这种先进的模型显示了改善药物毒性测试和识别肝功能新临床诊断标记的前景.

科学领域:

  • 肝病学 肝病学是一种肝病学.
  • 毒理学 毒理学 毒理学
  • 生物医学工程 生物医学工程

背景情况:

  • 当前的体外毒理学模型往往缺乏直接临床应用所需的翻译潜力.
  • 缩小临床前发现和临床结果之间的差距,需要更具生理相关性的实验系统.

研究的目的:

  • 开发和验证一个多细胞体外肝脏模型,准确地概述人类肝脏的微环境.
  • 通过比较其对已知药物效应的生理反应,观察到体内生物的作用,来评估开发模型的翻译潜力.
  • 确定肝功能新型临床诊断标记物的潜在细胞来源.

主要方法:

  • 在各种组合和条件下共同培养四种主要肝细胞类型 (肝细胞,肝星细胞,库弗弗细胞和肝侧侧内皮细胞).
  • 优化细胞培养基的组成,体积,细胞比例和细胞外矩阵的结合.
  • 优化体外模型对模型药物的暴露:利芬素 (RIF),易布洛芬 (IBU) 和5-甲 (5-FU).
  • 使用临床前和临床仪器在一周时间内分析微解剖学和生理学变化.

主要成果:

  • 确定了最佳的体外肝脏模型配置,证明了与临床诊断相比较的生物标志物值.
  • 在选择的模型中,暴露于RIF,IBU和5-FU导致葡萄糖,甘油三和白蛋白动态反映了临床数据中的体内观察.
关键词:
在体外毒性 in vitro毒性肝脏在体外模型中的体外模型.新的生物标志物 新的生物标志物翻译研究是翻译研究.

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  • 库弗弗细胞和肝侧鼻内皮细胞 (LSEC) 成为确定肝功能临床诊断标记物的有希望的候选人.

    • 结论:

    • 一个新的体外肝脏模型已经成功建立,紧密模仿本地肝脏微环境,并促进数据翻译.
    • 该模型在体内复制药物反应的能力表明其在临床前毒理学和药物开发中的实用性.
    • 该研究强调了库普费尔细胞和LSEC作为开发新临床生物标志物评估肝脏健康和功能的来源的潜力.