Modeling hepatic steatosis with human adult stem cell-derived liver organoids

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2025-05-16 Epub Date: 2025-04-03 DOI:10.1016/j.isci.2025.112344

Liuyang Zhu , Sen Liu , Ze Wang , Yueyue Yang , Pinsheng Han , Wen Tong , Tianyu Zhao , Libo Wang , Tao Cui , Long Yang , Yamin Zhang

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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) remains the most common chronic liver disease worldwide, and appropriate in vitro models are of great significance for investigating pathogenesis and drug screening of MASLD. In this study, human expandable cholangiocyte organoids were derived from adult stem cells of normal liver tissue. After differentiation, liver organoids (LOs) exhibited the functional characteristics and genomic features of mature hepatocytes. To induce steatosis, LOs were incubated with a gradient concentration oleic acid, and it was found that the model could recapitulate the development of lipid accumulation and inflammation. In addition, the drug sensitivity of the hepatic steatosis model was further verified through anti-steatosis drug testing. In summary, LOs have great potential for disease modeling, and the results indicate that the hepatic steatosis model may serve as a useful tool for exploring the molecular mechanisms and drug screening of MASLD.

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用人成体干细胞衍生的肝类器官模拟肝脂肪变性

代谢功能障碍相关脂肪变性肝病（MASLD）是世界范围内最常见的慢性肝病，合适的体外模型对于研究MASLD的发病机制和药物筛选具有重要意义。在本研究中，人类可扩展胆管细胞类器官来源于正常肝组织的成体干细胞。肝类器官（LOs）分化后表现出成熟肝细胞的功能特征和基因组特征。为了诱导脂肪变性，将LOs与梯度浓度油酸孵育，发现该模型可以再现脂质积累和炎症的发展。此外，通过抗脂肪变性药物试验进一步验证肝脂肪变性模型的药物敏感性。综上所述，LOs在疾病建模方面具有很大的潜力，结果表明肝脏脂肪变性模型可以作为探索MASLD分子机制和药物筛选的有用工具。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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