人工诱导多能干细胞（iPSC）来源的肝脏器官样体可作为器官生成、疾病、药物筛选和再生医学的模型。目前形成器官样体的主要方法依赖于Matrigel，其批次变异性和异源性来源对机理研究和转化为人类临床治疗构成挑战。本文研究证明，在旋转壁器皿（RWVs）中自组装的无Matrigel的iPSC衍生器官样体展示出比在Matrigel上形成的器官样体更好的肝细胞特异性功能。我们展示，RWVs通过消除对hepatic血系分化有负面影响的Matrigel的需要，在一定程度上产生高功能的肝脏器官样体。 RWV肝脏器官样体在长期培养中保持可持续的功能，并表达一系列成熟的功能基因，其水平可与成年人类肝脏相媲美，同时仍然保持一些胎儿特征。我们的结果表明，RWVs为形成适用于研究和临床应用的无Matrigel肝脏器官样体提供了简单和高通量的方法。 ©作者（们）2022年。由牛津大学出版社出版。

Human induced pluripotent stem cell (iPSC)-derived liver organoids serve as models of organogenesis, disease, drug screening, and regenerative medicine. Prevailing methods for generating organoids rely on Matrigel, whose batch-to-batch variability and xenogeneic source pose challenges to mechanistic research and translation to human clinical therapy. In this report, we demonstrate that self-assembled Matrigel-free iPSC-derived organoids developed in rotating wall vessels (RWVs) exhibit greater hepatocyte-specific functions than organoids formed on Matrigel. We show that RWVs produce highly-functional liver organoids in part by eliminating the need for Matrigel, which has adverse effects on hepatic lineage differentiation. RWV liver organoids sustain durable function over long-term culture and express a range of mature functional genes at levels comparable to adult human liver, while retaining some fetal features. Our results indicate that RWVs provide a simple and high-throughput way to generate Matrigel-free liver organoids suitable for research and clinical applications.© The Author(s) 2022. Published by Oxford University Press.