在临床前药物开发中人性化的肝脏小鼠模型:当前状态,翻译挑战和新兴技术
Xumiao Zhang1, Lu Lu1, Wei Xiao2
1Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Drug discovery today
|January 23, 2026
概括
人性化的肝脏小鼠模型通过模仿人类新陈代谢来改善药物测试. 新兴技术提高了对复杂肝病研究的准确性.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 肝病学 肝病学是一种肝病学.
- 药物开发 药物开发
背景情况:
- 人性化的肝脏小鼠模型将人类肝细胞植入免疫缺陷小鼠.
- 这些模型复制了人类的代谢和运输途径,有助于药物预测.
- 目前的限制包括缺乏肠道CYP3A4表达和免疫细胞.
研究的目的:
- 审查人性化的肝脏小鼠模型的应用和局限性.
- 突出新兴的提高模型忠实性的策略.
- 讨论模拟复杂肝脏疾病的潜力.
主要方法:
- 在免疫缺陷小鼠肝脏中移植初级人类肝细胞.
- 新兴技术的应用:双人化,非体细胞补充,3D生物打印,3D生物打印,患者衍生肝细胞.
- 与体外和计算平台的集成.
主要成果:
- 人性化的肝脏模型显著改善了对药理动力学,药物相互作用和肝毒性的预测.
- 这些模型用于MASLD/MASH,纤维化,HCC和病毒性肝炎的研究.
- 新兴的方法增强了翻译效率,减少了研发消耗.
结论:
- 人性化的肝脏小鼠模型是药物开发和肝脏疾病研究的宝贵工具.
- 模型构建和与其他平台集成的进步正在扩大它们的实用性.
- 这些改进的模型为研究复杂的代谢相关疾病提供了更大的潜力.
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