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Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo
In the liver, the bile canaliculi of hepatocytes are connected to intrahepatic bile ducts lined with cholangiocytes, which remove cytotoxic bile from the liver tissue. Although liver organoids have been reported, it is not clear whether the functional connection between hepatocytes and cholangiocyte...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185093/ https://www.ncbi.nlm.nih.gov/pubmed/34099675 http://dx.doi.org/10.1038/s41467-021-23575-1 |
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author | Tanimizu, Naoki Ichinohe, Norihisa Sasaki, Yasushi Itoh, Tohru Sudo, Ryo Yamaguchi, Tomoko Katsuda, Takeshi Ninomiya, Takafumi Tokino, Takashi Ochiya, Takahiro Miyajima, Atsushi Mitaka, Toshihiro |
author_facet | Tanimizu, Naoki Ichinohe, Norihisa Sasaki, Yasushi Itoh, Tohru Sudo, Ryo Yamaguchi, Tomoko Katsuda, Takeshi Ninomiya, Takafumi Tokino, Takashi Ochiya, Takahiro Miyajima, Atsushi Mitaka, Toshihiro |
author_sort | Tanimizu, Naoki |
collection | PubMed |
description | In the liver, the bile canaliculi of hepatocytes are connected to intrahepatic bile ducts lined with cholangiocytes, which remove cytotoxic bile from the liver tissue. Although liver organoids have been reported, it is not clear whether the functional connection between hepatocytes and cholangiocytes is recapitulated in those organoids. Here, we report the generation of a hepatobiliary tubular organoid (HBTO) using mouse hepatocyte progenitors and cholangiocytes. Hepatocytes form the bile canalicular network and secrete metabolites into the canaliculi, which are then transported into the biliary tubular structure. Hepatocytes in HBTO acquire and maintain metabolic functions including albumin secretion and cytochrome P450 activities, over the long term. In this study, we establish functional liver tissue incorporating a bile drainage system ex vivo. HBTO enable us to reproduce the transport of hepatocyte metabolites in liver tissue, and to investigate the way in which the two types of epithelial cells establish functional connections. |
format | Online Article Text |
id | pubmed-8185093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81850932021-06-11 Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo Tanimizu, Naoki Ichinohe, Norihisa Sasaki, Yasushi Itoh, Tohru Sudo, Ryo Yamaguchi, Tomoko Katsuda, Takeshi Ninomiya, Takafumi Tokino, Takashi Ochiya, Takahiro Miyajima, Atsushi Mitaka, Toshihiro Nat Commun Article In the liver, the bile canaliculi of hepatocytes are connected to intrahepatic bile ducts lined with cholangiocytes, which remove cytotoxic bile from the liver tissue. Although liver organoids have been reported, it is not clear whether the functional connection between hepatocytes and cholangiocytes is recapitulated in those organoids. Here, we report the generation of a hepatobiliary tubular organoid (HBTO) using mouse hepatocyte progenitors and cholangiocytes. Hepatocytes form the bile canalicular network and secrete metabolites into the canaliculi, which are then transported into the biliary tubular structure. Hepatocytes in HBTO acquire and maintain metabolic functions including albumin secretion and cytochrome P450 activities, over the long term. In this study, we establish functional liver tissue incorporating a bile drainage system ex vivo. HBTO enable us to reproduce the transport of hepatocyte metabolites in liver tissue, and to investigate the way in which the two types of epithelial cells establish functional connections. Nature Publishing Group UK 2021-06-07 /pmc/articles/PMC8185093/ /pubmed/34099675 http://dx.doi.org/10.1038/s41467-021-23575-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tanimizu, Naoki Ichinohe, Norihisa Sasaki, Yasushi Itoh, Tohru Sudo, Ryo Yamaguchi, Tomoko Katsuda, Takeshi Ninomiya, Takafumi Tokino, Takashi Ochiya, Takahiro Miyajima, Atsushi Mitaka, Toshihiro Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
title | Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
title_full | Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
title_fullStr | Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
title_full_unstemmed | Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
title_short | Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
title_sort | generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185093/ https://www.ncbi.nlm.nih.gov/pubmed/34099675 http://dx.doi.org/10.1038/s41467-021-23575-1 |
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