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营养环境改善了人类iPSC衍生的肝细胞和HepG2中的药物代谢活性

Victoria Pozo Garcia¹, Tuğçe S Çobanoğlu¹, Helen Sophie Hammer²

¹Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit (VU) Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, the Netherlands.

Archives of toxicology

|August 12, 2025

概括

这项研究增强了人类肝细胞样细胞 (HLC) 和代谢活跃的HepG2 (mHepG2) 用于药物代谢研究. 优化营养方案改善了体外肝脏模型,显示了mHepG2

科学领域:

肝病学和再生医学肝病学和再生医学
药物代谢和毒理学的药物代谢.
干细胞生物学干细胞生物学

背景情况:

人类诱导的多能干细胞 (iPSCs) 为肝脏研究和再生医学提供了潜力.
由于代谢功能有限,开发具有功能的人类iPSC衍生的肝细胞样细胞 (HLC) 是具有挑战性的.
像HepG2这样的现有细胞模型在代谢能力上有已知的局限性.

研究的目的:

描述和比较HLC和代谢增强的HepG2细胞系 (mHepG2) 的药物代谢活性.
为了研究营养饮食对这些体外肝脏模型代谢功能的影响.
评估关键药物代谢细胞P450 (CYP) 异酶的表达和活性.

主要方法:

利用适应营养方案培养HLCs和mHepG2细胞.
采用基于液态染色体质谱 (LC-MS) 的代谢学方法.
使用模型药物作为记者研究了11种与药物相关的CYP异酶的转录组,蛋白组和代谢组.

主要成果:

mHepG2表现出显著的药物代谢活性,特别是在8种药物代谢CYP上,表现优于其标准对应物.
HLCs在转录水平上表现出广泛的CYP覆盖范围和对各种化学攻击的弹性.
营养环境调节被确定为增强体外肝脏模型代谢功能的关键因素.

结论:

代谢活性HepG2 (mHepG2) 是用于药物代谢研究的高性能细胞模型.
由于其广泛的CYP覆盖范围,人类iPSC衍生的肝细胞样细胞 (HLC) 对个性化代谢研究具有前景.
优化营养环境对于改善体外肝脏模型的功能至关重要.

关键词:

细胞染色体P450 (CYP) 的使用药物代谢药物代谢诱导多能干细胞 (iPSCs) 是一种干细胞.在 LCMS 中使用.肝脏肝脏肝脏肝脏代谢学代谢学代谢学

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