Li Peilin, Miyamoto Daisuke, Huang Yu, Adachi Tomohiko, Hidaka Masaaki, Hara Takanobu, Soyama Akihiko, Matsushima Hajime, Imamura Hajime, Kanetaka Kengo, Gu Weili, Eguchi Susumu
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
Front Bioeng Biotechnol. 2023 Aug 21;11:1249769. doi: 10.3389/fbioe.2023.1249769. eCollection 2023.
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 research. The aim of the present study was to establish three-dimensional BDs combined with human mature hepatocytes (hMHs) using chemically induced human liver progenitor cells (hCLiPs) derived from hMHs. 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. We present a novel three-dimensional BD combined with hMHs for study, drug screening and the therapeutic modulation of the cholangiocyte function.
肝内胆管在胆汁的修饰和运输中起重要作用，胆管与肝细胞之间的整合是肝功能的基础。然而，胆管细胞来源的缺乏限制了研究。本研究的目的是利用源自人成熟肝细胞（hMHs）的化学诱导人肝祖细胞（hCLiPs）建立三维胆管与人成熟肝细胞的组合。在本研究中，我们使用肝细胞生长因子和细胞外基质从hCLiPs形成功能性胆管。胆管表达典型的胆管标志物CK-7、GGT1、CFTR和EpCAM，并能够将胆汁样物质罗丹明123转运到管腔中。将建立的三维胆管与hMHs共培养。这些细胞能够与胆管结合，胆汁酸类似物CLF从培养基中通过hMHs转运并积聚在胆管的管腔中。当与hMHs连接时，由hCLiPs产生的胆管显示出胆管功能和生理系统（例如，肝脏内胆汁的运输）。我们提出了一种新型的三维胆管与hMHs的组合用于研究、药物筛选和胆管细胞功能的治疗调节。
