Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system
Abstract Examining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For cocultur...
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Nature Portfolio
2021
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oai:doaj.org-article:f3d6e51115fc431c979b3b6a3eb9921c2021-12-02T13:30:11ZCoculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system10.1038/s41598-021-84861-y2045-2322https://doaj.org/article/f3d6e51115fc431c979b3b6a3eb9921c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84861-yhttps://doaj.org/toc/2045-2322Abstract Examining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance and careful handling. Herein, we demonstrated the potential of coculturing normal cells on MPSs in the evaluation of intestine–liver interactions. To this end, we cocultured human-induced pluripotent stem cell-derived intestinal cells and fresh human hepatocytes which were isolated from PXB mice with medium circulation in a pneumatic-pressure-driven MPS with pipette-friendly liquid-handling options. The cytochrome activity, albumin production, and liver-specific gene expressions in human hepatocytes freshly isolated from a PXB mouse were significantly upregulated via coculture with hiPS-intestinal cells. Our normal cell coculture shows the effects of the interactions between the intestine and liver that may occur in vivo. This study is the first to demonstrate the coculturing of hiPS-intestinal cells and fresh human hepatocytes on an MPS for examining pure inter-organ interactions. Normal-cell coculture using the multi-organ MPS could be pursued to explore unknown physiological mechanisms of inter-organ interactions in vitro and investigate the physiological response of new drugs.Marie ShinoharaHiroshi ArakawaYuuichi OdaNobuaki ShirakiShinji SugiuraTakumi NishiuchiTaku SatohKeita IinoSylvia LeoYusuke KatoKarin ArayaTakumi KawanishiTomoki NakatsujiManami MitsutaKosuke InamuraTomomi GotoKenta ShinhaWataru NiheiKikuo KomoriMasaki NishikawaShoen KumeYukio KatoToshiyuki KanamoriYasuyuki SakaiHiroshi KimuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Marie Shinohara Hiroshi Arakawa Yuuichi Oda Nobuaki Shiraki Shinji Sugiura Takumi Nishiuchi Taku Satoh Keita Iino Sylvia Leo Yusuke Kato Karin Araya Takumi Kawanishi Tomoki Nakatsuji Manami Mitsuta Kosuke Inamura Tomomi Goto Kenta Shinha Wataru Nihei Kikuo Komori Masaki Nishikawa Shoen Kume Yukio Kato Toshiyuki Kanamori Yasuyuki Sakai Hiroshi Kimura Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| description |
Abstract Examining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance and careful handling. Herein, we demonstrated the potential of coculturing normal cells on MPSs in the evaluation of intestine–liver interactions. To this end, we cocultured human-induced pluripotent stem cell-derived intestinal cells and fresh human hepatocytes which were isolated from PXB mice with medium circulation in a pneumatic-pressure-driven MPS with pipette-friendly liquid-handling options. The cytochrome activity, albumin production, and liver-specific gene expressions in human hepatocytes freshly isolated from a PXB mouse were significantly upregulated via coculture with hiPS-intestinal cells. Our normal cell coculture shows the effects of the interactions between the intestine and liver that may occur in vivo. This study is the first to demonstrate the coculturing of hiPS-intestinal cells and fresh human hepatocytes on an MPS for examining pure inter-organ interactions. Normal-cell coculture using the multi-organ MPS could be pursued to explore unknown physiological mechanisms of inter-organ interactions in vitro and investigate the physiological response of new drugs. |
| format |
article |
| author |
Marie Shinohara Hiroshi Arakawa Yuuichi Oda Nobuaki Shiraki Shinji Sugiura Takumi Nishiuchi Taku Satoh Keita Iino Sylvia Leo Yusuke Kato Karin Araya Takumi Kawanishi Tomoki Nakatsuji Manami Mitsuta Kosuke Inamura Tomomi Goto Kenta Shinha Wataru Nihei Kikuo Komori Masaki Nishikawa Shoen Kume Yukio Kato Toshiyuki Kanamori Yasuyuki Sakai Hiroshi Kimura |
| author_facet |
Marie Shinohara Hiroshi Arakawa Yuuichi Oda Nobuaki Shiraki Shinji Sugiura Takumi Nishiuchi Taku Satoh Keita Iino Sylvia Leo Yusuke Kato Karin Araya Takumi Kawanishi Tomoki Nakatsuji Manami Mitsuta Kosuke Inamura Tomomi Goto Kenta Shinha Wataru Nihei Kikuo Komori Masaki Nishikawa Shoen Kume Yukio Kato Toshiyuki Kanamori Yasuyuki Sakai Hiroshi Kimura |
| author_sort |
Marie Shinohara |
| title |
Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| title_short |
Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| title_full |
Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| title_fullStr |
Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| title_full_unstemmed |
Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| title_sort |
coculture with hips-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/f3d6e51115fc431c979b3b6a3eb9921c |
| work_keys_str_mv |
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