一个可扩展和成熟的hiPSC衍生的肝脏有机体的生成和应用
Sen Liu1,2,3, Ze Wang2,4, Liuyang Zhu5
1Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
Acta pharmaceutica Sinica. B
|January 1, 2026
概括
我们开发了一种新的方法,从人类诱导的多能干细胞中制造成熟的肝脏内皮器官 (SB-HEOs). 这些有机物改善肝病建模,药物测试和再生医学应用.
科学领域:
- 肝病学和再生医学 肝病学和再生医学
- 干细胞生物学和有机体技术
背景情况:
- 器官对肝脏疾病建模有价值,但与功能性肝细胞的可再生生成作斗争.
- 现有的方法在制造成熟的肝脏器官中缺乏效率和可重复性.
研究的目的:
- 建立一个高效和可复制的协议,从hiPSC衍生的肝脏内皮细胞生成功能成熟的肝脏内皮器官 (SB-HEOs).
- 为各种生物医学应用验证SB-HEO的成熟度和功能.
主要方法:
- 利用一种新的方法,涉及SB431542/BMP4治疗hiPSC衍生的肝脏内皮细胞.
- 通过转录组分析和功能表达检测确认了有机体成熟.
- 应用SB-HEO来评估药物诱导性肝损伤 (DILI),非酒精性脂肪肝炎 (NASH) 模型,药物代谢,并重新填充FRG小鼠.
主要成果:
- 成功生成具有扩展和成熟能力的功能成熟的SB-HEO.
- 证明了高药物代谢能力,延长FRG小鼠的存活时间.
- 准确识别了肝毒性和非肝毒性药物,并模仿了与代谢功能障碍相关的脂肪性肝病.
- 展示了高CYP450活性,对于药物测试和再生医学至关重要.
结论:
- SB-HEOs代表了一种用于毒理学测试,药物代谢研究,肝病建模和再生医学的新型细胞系统.
- SB-HEOs的高CYP450活性为药物开发和个性化治疗提供了显著的潜力.
- 该协议提供了一种可复制和有效的方法来产生成熟的肝脏器官.
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