Several three‐dimensional cell culture systems are currently available to create liver organoids. In gneral, these systems display better physiologic and metabolic aspects of intact liver tissue compared with two‐dimensional culture systems. However, none reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self‐assembled inside acellular liver extracellular matrix scaffolds to form three‐dimensional liver organoids that recapitulated several aspects of hepatobiliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures. The duct morphogenesis process was interrupted by inhibiting Notch signaling, in an attempt to create a liver developmental disease model with a similar phenotype to Alagille syndrome. Conclusion: In the current study, we created an in vitro model of human liver development and disease, physiology, and metabolism, supported by liver extracellular matrix substrata; we envision that it will be used in the future to study mechanisms of hepatic and biliary development and for disease modeling and drug screening. (Hepatology 2018;67:750‐761).

中文翻译：

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自组装肝脏类器官在体外重现肝胆器官发生

目前有几种三维细胞培养系统可用于创建肝脏类器官。一般而言，与二维培养系统相比，这些系统显示出完整肝组织更好的生理和代谢方面。然而，没有一个能够可靠地模拟人类肝脏发育，包括肝细胞和胆管细胞解剖结构的平行形成。在这里，我们展示了人胎肝祖细胞在脱细胞肝细胞外基质支架内自组装形成三维肝脏类器官，概括了肝胆器官发生的几个方面，并导致逐渐分化的肝细胞和胆管结构的伴随形成。导管形态发生过程因抑制 Notch 信号而中断，试图创建一个与 Alagille 综合征表型相似的肝脏发育疾病模型。结论：在目前的研究中，我们创建了一个由肝细胞外基质支持的人类肝脏发育和疾病、生理和代谢的体外模型；我们设想它在未来将用于研究肝脏和胆道发育的机制以及疾病建模和药物筛选。（肝病学 2018 年；67：750-761）。