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在肝脏微生理系统PhysioMimix LC12和96井板中对特定物种肝细胞功能和药物效应的比较分析

Chander K Negi¹, Courtney Sakolish¹, Han-Hsuan D Tsai¹

¹Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843, United States.

ACS pharmacology & translational science

|November 20, 2025

概括

这项研究表明,微生理系统 (MPS) 可以预测跨物种的药物诱导性肝损伤 (DILI). 在MPS中的肝脏模型显示稳定的功能,并反映了体内毒性,有助于临床前安全性评估.

科学领域:

毒理学毒理学毒理学
药物开发药物开发
在 Vitro 模型中

背景情况:

药物诱导性肝损伤 (DILI) 是药物开发中的一个重大障碍.
肝脏毒性的物种间差异使临床前安全性评估复杂化.
微生理系统 (MPS) 提供了预测特定物种毒性的潜力.

研究的目的:

评估PhysioMimix LC12 MPS对评估特定物种DILI的有用性.
将MPS性能与传统的二维细胞培养进行比较.
为了研究药物诱导的肝毒性,使用来自人类,子,老鼠和狗的初级肝细胞.

主要方法:

来自四种物种的初级肝细胞在PhysioMimix LC12 MPS和2D培养物中培养长达14天.
分析了功能 (白蛋白,尿素),表型和转录的概况.
细胞被暴露在已知的肝毒剂 (博森坦,菲亚鲁丁,普罗马) 中,以评估物种特异性反应.

主要成果:

与2D培养相比,PhysioMimix LC12 MPS保持了更稳定的白蛋白和尿素生产.
在两种模型中观察到细胞和分子对药物反应的特定物种差异.
来自MPS的数据准确地反映了动物和人类预期的毒理效应.

结论:

该PhysioMimix LC12 MPS是肝脏安全研究的一个有价值的工具,能够评估物种特定的DILI.
MPS模型提供了从临床前数据预测人类毒性的见解.
解决MPS变化和吞吐量限制是未来前性研究的关键.

关键词:

物理模拟器 LC1212 交叉物种 DILI DILI 的意思微生理系统的微生理系统.

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