Coculture with HiPS-derived Intestinal Cells Enhanced Human Hepatocyte Functions in a Pneumatic-pressure-driven Two-organ Microphysiological System

Overview

Journal Sci Rep

Specialty Science

Date 2021 Mar 9

PMID 33686099

Citations 9

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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