In vitro reconstruction of functional bile canaliculus-intrahepatic bile duct structure

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19932
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kyushu University (2019-2020); Nagasaki University (2018)
• Principal Investigator: SAKAI Yusuke 九州大学, 工学研究院, 助教 (10608904)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: 肝細胞 / 胆管 / 肝毛細胆管 / リプログラミング / 再生医療 / 肝臓

Outline of Final Research Achievements

The excretion system of bile accumulated in the hepatic bile canaliculus must be reconstructed for fabrication of the 3D liver tissue in vitro. In this study, the bile excretion system was reconstructed by combining hepatocyte tissue culture and bile duct preparation. The cultured bile ducts are prepared from CLiPs (chemically-induced liver progenitors) reprogrammed from primary hepatocytes based on the previous report,, and co-cultured with human and rat primary hepatocytes. The integrated tissue excreted bile acid-like fluorescent reagents, it means that the hepatic bile canaliculus formed between hepatocytes functionally connected with cultured bile duct. Liver-specific gene expression was enhanced by co-culture. This technology is expected to be applied to a liver model for drug screening and a regenerative medicine in the future.

Free Research Field

再生医工学

Academic Significance and Societal Importance of the Research Achievements

肝毛細胆管と胆管を機能的に接合したモデルはこれまでに報告されておらず、誰も成し得なかった挑戦的かつ世界初の研究である。特に手術検体より得たヒト初代肝細胞を用いた点は、本研究の特徴である。組織工学（再生医療）分野や薬物代謝アッセイツールとして、学術面・社会面の双方に強いインパクトを与え得る。