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.
Department of Hepatobiliary and Pancreatic Surgery and Liver Transplant Center, the First Hospital of Shanxi Medical University, Taiyuan 030001, China.
Acta Biochim Biophys Sin (Shanghai). 2024 May 30;56(10):1460-1472. doi: 10.3724/abbs.2024074.
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.
酒精性肝病（ALD）是一个重大的健康挑战，因此需要进行全面的研究工作，以增进我们对ALD 的认识并制定治疗策略。然而，由于现有的肝脏疾病模型存在局限性，有效的治疗方法的开发受到了阻碍。肝脏类器官具有细胞复杂性和与人类肝脏非常相似的三维（3D）组织结构，是肝脏疾病研究的理想模型。在这项研究中，我们使用精心设计的方案，从人诱导多能干细胞（hiPSC）分化为肝脏类器官。该方案在 3D 培养系统中精确组合细胞因子和小分子化合物，以指导分化过程。随后，将这些分化的肝脏类器官进行乙醇处理以诱导 ALD，从而建立疾病模型。通过一系列实验的严格评估表明，该模型部分再现了临床 ALD 中观察到的关键病理特征，包括细胞线粒体损伤、细胞活性氧（ROS）水平升高、脂肪肝和肝细胞坏死。此外，该模型可用于筛选治疗 ALD 的药物。总之，来源于 hiPSC 分化的 ALD 肝脏类器官模型为在临床环境中推进我们对 ALD 的认识和管理提供了一个宝贵的平台。
