TY - JOUR
T1 - Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
AU - Saito, Yoshimasa
AU - Nakaoka, Toshiaki
AU - Muramatsu, Toshihide
AU - Ojima, Hidenori
AU - Sukeda, Aoi
AU - Sugiyama, Yuko
AU - Uchida, Ryoei
AU - Furukawa, Ryo
AU - Kitahara, Aya
AU - Sato, Toshiro
AU - Kanai, Yae
AU - Saito, Hidetsugu
N1 - Funding Information:
This work was supported by a Keio University Special Grant-in-Aid for Innovative Collaborative Research Projects (to Y. Saito), a Grant-in-Aid for Scientific Research B (26290049) from the Japan Society for Promotion of Science (to Y. Saito), and the Inaida Fund (to H. Saito).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-018-21121-6
DO - 10.1038/s41598-018-21121-6
M3 - Article
C2 - 29434290
AN - SCOPUS:85041944454
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 2821
ER -
