Development of an alcoholic liver disease model for drug evaluation from human induced pluripotent stem cellderived liver organoids  

作　　者：Zhiwei Feng Bingrui Zhou Qizhi Shuai Yunliang Wei Ning Jin Xiaoling Wang Hong Zhao Zhizhen Liu Jun Xu Jianbing Mu Jun Xie 

机构地区：[1]Department of Biochemistry and Molecular Biology,Shanxi Key Laboratory of Birth Defect and Cell Regeneration,MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention,Shanxi Medical University,Taiyuan 030001,China [2]Department of Hepatobiliary and Pancreatic Surgery and Liver Transplant Center,the First Hospital of Shanxi Medical University,Taiyuan 030001,China [3]Laboratory of Malaria and Vector Research,National Institute of Allergy and Infectious Diseases,National Institutes of Health,12735 Twinbrook Parkway,USA

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第10期1460-1472,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Fund of Shanxi″1331 Project″Key Subjects Construction(No.1331KSC);the Fund of Science and Technology Innovation Plan for Colleges and Universities from Education Department of Shanxi Province(No.2019L0423);the Key R&D Program of Shanxi Province(International Cooperation,No.201903D421023);the Shanxi Basic Research Program(Nos.20210302124406 and 202103021223227).

摘　　要：Alcoholic liver disease(ALD)poses a significant health challenge,so comprehensive research efforts to improve our understanding and treatment strategies are needed.However,the development of effective treatments is hindered by the limitation of existing liver disease models.Liver organoids,characterized by their cellular complexity and three-dimensional(3D)tissue structure closely resembling the human liver,hold promise as ideal models for liver disease research.In this study,we use a meticulously designed protocol involving the differentiation of human induced pluripotent stem cells(hiPSCs)into liver organoids.This process incorporates a precise combination of cytokines and small molecule compounds within a 3D culture system to guide the differentiation process.Subsequently,these differentiated liver organoids are subject to ethanol treatment to induce ALD,thus establishing a disease model.A rigorous assessment through a series of experiments reveals that this model partially recapitulates key pathological features observed in clinical ALD,including cellular mitochondrial damage,elevated cellular reactive oxygen species(ROS)levels,fatty liver,and hepatocyte necrosis.In addition,this model offers potential use in screening drugs for ALD treatment.Overall,the liver organoid model of ALD,which is derived from hiPSC differentiation,has emerged as an invaluable platform for advancing our understanding and management of ALD in clinical settings.

关 键 词：human induced pluripotent stem cell liver organoid alcoholic liver disease drug screening 

分 类 号：R575[医药卫生—消化系统]