生体肝組織と同様な連続的胆汁排泄をin vitroで再現

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2026-04-01 東京大学

東京大学などの研究チームは、培養肝細胞から胆汁成分を生体同様に連続的に排泄・回収できる新規デバイスを開発した。微細加工技術と細胞極性制御を組み合わせ、マイクロ流路へ胆汁を連続排出させる仕組みを実現し、従来法に比べ約13.7倍の高濃度で非侵襲的に回収することに成功した。これにより、これまで困難だったin vitroでの肝臓の生理機能再現が可能となり、薬物動態解析や肝疾患研究への応用が期待される画期的成果である。

生体肝組織と同様な連続的胆汁排泄をin vitroで再現
培養肝細胞が分泌した胆汁成分の連続的排泄を可能とする新規肝細胞培養デバイス

<関連情報>

マイクロチャネルパターンデバイス上の極性化肝細胞からの胆汁の連続排出 Continuous bile excretion from polarized hepatocytes on a microchannel-patterned device

Fumiya Tokito ∙ Hiroshi Arakawa ∙ Yuya Nakazono ∙ … ∙ Takeshi Katsuda ∙ Masaki Nishikawa ∙ Yasuyuki Sakai
Cell Reports Physical Science  Published:March 31, 2026
DOI:https://doi.org/10.1016/j.xcrp.2026.103229

Highlights

  • Microchannel-patterned device enables continuous bile drainage from hepatocytes
  • Hepatocyte polarization via CLDN1 increases bile metabolite yield 1.8-fold
  • Device collects 13.7-fold higher bile metabolite concentrations than previous methods

Summary

Continuous bile excretion is crucial for maintaining liver physiology. However, current in vitro liver culture models lack a bile drainage system, thus preventing the continuous bile excretion observed in vivo. In this study, we aim to recapitulate continuous bile excretion in the liver by developing a microchannel-patterned device through microfabrication technology. Using this device, we successfully achieved the continuous drainage and collection of bile acids from primary hepatocytes via microchannels. Furthermore, the polarization of hepatocytes via CLDN1 facilitates the formation of “open” bile canaliculi between the hepatocytes and the culture surface, increasing the amount of biliary metabolites excreted into the microchannels by 1.8-fold. Finally, the concentration of biliary metabolites collected using this device is 13.7-fold greater than that obtained with conventional bile recovery methods. This hepatocyte culture platform represents a major step toward the recapitulation of liver physiology, with applications in pharmacology and liver disease research.

生物化学工学
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