Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo, 105-8512, Japan.
Division of Gastroenterology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Sci Rep. 2018 Feb 12;8(1):2821. doi: 10.1038/s41598-018-21121-6.
Intrahepatic cholangiocarcinoma (IHCC) is a highly aggressive malignancy with a poor prognosis. It is thought to originate from cholangiocytes, which are the component cells of intrahepatic bile ducts. However, as patients with viral hepatitis often develop IHCC, it has been suggested that transformed hepatocytes may play a role in IHCC development. To investigate whether IHCC cells can be converted to functional hepatocytes, we established organoids derived from human IHCC and cultured them under conditions suitable for hepatocyte differentiation. IHCC organoids after hepatocyte differentiation acquired functions of mature hepatocytes such as albumin secretion, bile acid production and increased CYP3A4 activity. Studies using a mouse model of IHCC indicate that Wnt3a derived from macrophages recruited upon inflammation in the liver may promote the malignant transformation of hepatocytes to IHCC cells. The results of the present study support the recently proposed hypothesis that IHCC cells are derived from hepatocytes.
肝内胆管癌（IHCC）是一种侵袭性很强且预后较差的恶性肿瘤。它被认为起源于胆管细胞，胆管细胞是肝内胆管的组成细胞。然而，由于患有病毒性肝炎的患者常常会发展为 IHCC，因此有人认为转化的肝细胞可能在 IHCC 的发展中发挥作用。为了研究 IHCC 细胞是否可以转化为功能性肝细胞，我们建立了源自人 IHCC 的类器官，并在适合肝细胞分化的条件下对其进行培养。分化后的 IHCC 类器官获得了成熟肝细胞的功能，如白蛋白分泌、胆汁酸生成和 CYP3A4 活性增加。使用 IHCC 小鼠模型的研究表明，炎症时招募到肝脏的巨噬细胞中产生的 Wnt3a 可能促进了肝细胞向 IHCC 细胞的恶性转化。本研究的结果支持了最近提出的假说，即 IHCC 细胞来源于肝细胞。
