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为肝脏代谢研究生成和表征成熟的肝细胞有机体

Yuchen Liu¹, Yaxing Zhou¹, James Ahodantin²

¹Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA 02115, USA.

Journal of cell science

|May 3, 2024

概括

研究人员开发了具有成人肝功能的成熟肝细胞器官 (MHO). 这些MHO对于研究肝脏疾病和体外代谢调节有价值.

科学领域:

肝病学肝病学是一种肝病学.
在体外模型模型.
肝脏的再生再生

背景情况:

现有的肝细胞有机体 (HOs) 通常是胎儿的,缺乏成人代谢功能.
这限制了它们在代谢调节研究和肝脏疾病治疗中的使用.
对于准确的成人肝脏建模,需要成熟的肝细胞有机体 (MHO).

研究的目的:

开发新的培养条件,以产生具有成人代谢功能的成熟肝细胞有机体 (MHO).
从老鼠和人类来源建立MHO.
为了证明MHOs在研究肝脏生理学和疾病中的实用性.

主要方法:

优化培养条件使用trioidothyronine (T3) 和移除生长因子.
从小鼠和人类胎儿肝细胞生成MHO.
评估代谢功能,疾病建模和病毒感染.

主要成果:

成功生成具有成人肝脏代谢功能的成熟肝细胞有机体 (MHO).
MHOs表现出关键功能,如胆汁和尿素的生产,以及区域基因表达.
模拟MHO酒精性和非酒精性脂肪肝疾病,并显示改善的乙型肝炎病毒感染.
来自人类胎儿肝细胞的MHOs显示增强了B型肝炎病毒感染.

结论:

新的培养条件产生成熟的肝细胞有机体 (MHOs),具有成人肝功能.
MHO作为一个强大的体外模型,用于人类肝脏生理学和疾病研究.
人类MHO为肝脏疾病的治疗开发提供了一个强大的平台.

关键词:

胆汁酸代谢胆汁酸代谢乙型肝炎病毒的感染.肝细胞的有机体代谢性肝病是一种代谢性肝病.

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