Author:
Shinohara Marie,Arakawa Hiroshi,Oda Yuuichi,Shiraki Nobuaki,Sugiura Shinji,Nishiuchi Takumi,Satoh Taku,Iino Keita,Leo Sylvia,Kato Yusuke,Araya Karin,Kawanishi Takumi,Nakatsuji Tomoki,Mitsuta Manami,Inamura Kosuke,Goto Tomomi,Shinha Kenta,Nihei Wataru,Komori Kikuo,Nishikawa Masaki,Kume Shoen,Kato Yukio,Kanamori Toshiyuki,Sakai Yasuyuki,Kimura Hiroshi
Abstract
AbstractExamining 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.
Publisher
Springer Science and Business Media LLC
Cited by
17 articles.
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