多个血统的肝脏器官显示有毒的外体介导间接肝毒性
Lei Sun1,2, Yuying Zhang1, Yudi Niu1
1School of Biomedical Engineering, Tsinghua Medicine, Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Nature communications
|February 19, 2026
概括
伊米普拉米因向肝细胞发送有毒外体而导致间接肝损伤. 这项研究揭示了药物诱导的肝损伤的新机制以及用于药物查的新型有机体模型.
科学领域:
- 药物开发 药物开发
- 肝毒性 肝毒性 肝毒性
- 干细胞生物学 干细胞生物学
背景情况:
- 由于评估工具有限,间接肝毒性在药物开发中带来了挑战.
- 了解药物诱导的肝损伤机制对于更安全的治疗方法至关重要.
研究的目的:
- 开发一种新的有机体平台,用于评估药物诱导的肝损伤.
- 为了确定依赖于伊米普拉诱导的间接肝毒性背后的机制.
主要方法:
- 从人类胚胎干细胞中构建的3D多谱系肝脏器官.
- 使用有机体模型选了58种肝毒药物.
- 在体外和体内研究了伊米普拉的分子标和下游效应.
主要成果:
- 鉴定出伊米普拉是间接肝毒性的诱导剂.
- 发现的伊米普拉通过氨酸激酶受体B激活肝细胞,导致有毒的外体细胞形成.
- 已证明微RNA-34a-3p通过外体介导转移到肝细胞,导致细胞亡.
结论:
- 建立了一个生物模拟器官平台,用于精确的药物测试.
- 强调了细胞间通信在药物诱导的肝损伤中的关键作用.
- 发现了一种新的途径,用于因伊米胺诱导的肝毒性,涉及有毒的外体.
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