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

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...

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Autores principales:	Yoshimasa Saito, Toshiaki Nakaoka, Toshihide Muramatsu, Hidenori Ojima, Aoi Sukeda, Yuko Sugiyama, Ryoei Uchida, Ryo Furukawa, Aya Kitahara, Toshiro Sato, Yae Kanai, Hidetsugu Saito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f69bc81672bf4ab595b91a7b1a8952f1
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spelling	oai:doaj.org-article:f69bc81672bf4ab595b91a7b1a8952f12021-12-02T15:08:41ZInduction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system10.1038/s41598-018-21121-62045-2322https://doaj.org/article/f69bc81672bf4ab595b91a7b1a8952f12018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21121-6https://doaj.org/toc/2045-2322Abstract 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.Yoshimasa SaitoToshiaki NakaokaToshihide MuramatsuHidenori OjimaAoi SukedaYuko SugiyamaRyoei UchidaRyo FurukawaAya KitaharaToshiro SatoYae KanaiHidetsugu SaitoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshimasa Saito Toshiaki Nakaoka Toshihide Muramatsu Hidenori Ojima Aoi Sukeda Yuko Sugiyama Ryoei Uchida Ryo Furukawa Aya Kitahara Toshiro Sato Yae Kanai Hidetsugu Saito Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
description	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.
format	article
author	Yoshimasa Saito Toshiaki Nakaoka Toshihide Muramatsu Hidenori Ojima Aoi Sukeda Yuko Sugiyama Ryoei Uchida Ryo Furukawa Aya Kitahara Toshiro Sato Yae Kanai Hidetsugu Saito
author_facet	Yoshimasa Saito Toshiaki Nakaoka Toshihide Muramatsu Hidenori Ojima Aoi Sukeda Yuko Sugiyama Ryoei Uchida Ryo Furukawa Aya Kitahara Toshiro Sato Yae Kanai Hidetsugu Saito
author_sort	Yoshimasa Saito
title	Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
title_short	Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
title_full	Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
title_fullStr	Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
title_full_unstemmed	Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
title_sort	induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f69bc81672bf4ab595b91a7b1a8952f1
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Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system

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