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Abstract：
Background: The intrahepatic bile ducts (BDs) play an important role in the modification and transport of bile, and the integration between the BD and hepatocytes is the basis of the liver function. However, the lack of a source of cholangiocytes limits in vitro research. The aim of the present study was to establish three-dimensional BDs combined with human mature hepatocytes (hMHs) in vitro using chemically induced human liver progenitor cells (hCLiPs) derived from hMHs. Methods: In this study, we formed functional BDs from hCLiPs using hepatocyte growth factor and extracellular matrix. BDs expressed the typical biliary markers CK-7, GGT1, CFTR and EpCAM and were able to transport the bile-like substance rhodamine 123 into the lumen. The established three-dimensional BDs were cocultured with hMHs. These cells were able to bind to the BDs, and the bile acid analog CLF was transported from the culture medium through the hMHs and accumulated in the lumen of the BDs. The BDs generated from the hCLiPs showed a BD function and a physiological system (e.g., the transport of bile within the liver) when they were connected to the hMHs. Conclusion: We present a novel in vitro three-dimensional BD combined with hMHs for study, drug screening and the therapeutic modulation of the cholangiocyte function.
摘要：
背景:肝内胆管在胆汁的修饰和运输中起重要作用,BD与肝细胞之间的整合是肝功能的基础。然而,缺乏胆管细胞来源限制了体外研究。本研究的目的是使用源自hMHs的化学诱导的人肝祖细胞（hCLiPs）在体外建立与人成熟肝细胞（hMHs）结合的三维BD。方法:在本研究中,我们使用肝细胞生长因子和细胞外基质从hCLiPs形成功能性BD。BD表达典型的胆道标志物CK-7，GGT1，CFTR和EpCAM，并且能够将胆汁样物质罗丹明123运输到管腔中。将建立的三维BD与hMHs共培养。这些细胞能够与BD结合，胆汁酸类似物CLF从培养基中转运通过hMHs并积累在BD的内腔中。从hCLiPs产生的BD显示出BD功能和生理系统(例如，胆汁在肝脏内的运输），当它们与hMHs连接时。结论:我们提出了一种新型的体外三维BD结合hMHs进行研究,药物筛选和胆管细胞功能的治疗性调节。
