Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system

Yoshimasa Saito, Toshiaki Nakaoka, Toshihide Muramatsu, Hidenori Ojima, Aoi Sukeda, Yuko Sugiyama, Ryoei Uchida, Ryo Furukawa, Aya Kitahara, Toshiro Sato, Yae Kanai, Hidetsugu Saito

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number2821
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Organoids
Cholangiocarcinoma
Hepatocytes
Intrahepatic Bile Ducts
Cytochrome P-450 CYP3A
Cellular Structures
Bile Acids and Salts
Hepatitis
Albumins
Macrophages
Inflammation

ASJC Scopus subject areas

  • General

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Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system. / Saito, Yoshimasa; Nakaoka, Toshiaki; Muramatsu, Toshihide; Ojima, Hidenori; Sukeda, Aoi; Sugiyama, Yuko; Uchida, Ryoei; Furukawa, Ryo; Kitahara, Aya; Sato, Toshiro; Kanai, Yae; Saito, Hidetsugu.

In: Scientific Reports, Vol. 8, No. 1, 2821, 01.12.2018.

Research output: Contribution to journalArticle

Saito, Yoshimasa ; Nakaoka, Toshiaki ; Muramatsu, Toshihide ; Ojima, Hidenori ; Sukeda, Aoi ; Sugiyama, Yuko ; Uchida, Ryoei ; Furukawa, Ryo ; Kitahara, Aya ; Sato, Toshiro ; Kanai, Yae ; Saito, Hidetsugu. / Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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AU - Sukeda, Aoi

AU - Sugiyama, Yuko

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