Development of the innovative hybrid artificial liver with establishment of the hepatocyte strain from human iPS cells

• Project/Area Number: 25462093
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: National Hospital Organization, Kyushu Cancer Center (2015); Kyushu University (2013)
• Principal Investigator: YAMASHITA YOICHI 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, その他 (00404070)
• Co-Investigator(Kenkyū-buntansha): Yonemitsu Yoshikazu 九州大学, 薬学研究院, 教授 (40315065) ; Ikeda Tetsuo 九州大学, 医学研究院, 准教授 (60585701) ; Shirabe Ken 九州大学, 医学研究院, 准教授 (70264025) ; Maehara Yoshihiko 九州大学, 医学研究院, 教授 (80165662)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ヒトiPS細胞 / ハイブリッド型人工肝臓 / 人工肝臓

Outline of Final Research Achievements

We newly established the well-differentiated liver cell line which has ammonia metabolism from human iPS cells. The metabolic detoxification ability is one of the highest specific liver functions, therefore, this cell line is thought to be the leading cell source at the time of clinical application of the artificial liver support system.
The ultimate hybrid artificial liver should be a “dropper type” rather than an extracorporeal type, therefore, we used the decellularized liver as a scaffold. Because of the vulnerability of the outer wall of the decellularized liver, the reinforcement using the “polyglycolic acid sheet + fibrin/thrombin solution” was performed. We succeeded the extracorporeal circulation for approximately one hour of rat decellularized liver. Using this experimental system, we evaluated the functions of the rat decellularized liver implanted with rat primary hepatocytes, and confirmed the high rate of ammonia metabolism.

Research Products

• [Journal Article] Surgical results for recurrent hepatocellular carcinoma after curative hepatectomy: Repeat hepatectomy vs. salvage living donor livertransplantation. (2015)
  • Author(s): Yamashita Y, Yoshida Y, Kurihara T, Itoh S, Harimoto N, Ikegami T, Yoshizumi T, Uchiyama H, Shirabe K, Maehara Y.
  • Journal Title: Liver Transpl. Volume: 21 Pages: 961-8
  • Peer Reviewed
• [Journal Article] Surgical Outcomes of Hepatic Resection for Hepatitis B Virus Surface Antigen-Negative and Hepatitis C Virus Antibody-Negative Hepatocellular Carcinoma. (2015)
  • Author(s): Yamashita YI, Imai D, Bekki Y, Kimura K, Matsumoto Y, Nakagawara H, kegami T, Yoshizumi T, Shirabe K, Aishima S, Maehara Y
  • Journal Title: Ann Surgical Oncol Volume: 22 Pages: 2279-85
  • Peer Reviewed
• [Presentation] Fundamental technology for the creation of Whole Liver Engineering, and (2015)
  • Author(s): Yo-ichi Yamashita他7名
  • Organizer: 2015 4th Tissue Engineering and Regenerative Medicine International Society World Congress
  • Place of Presentation: Boston Marriott Copley Place Boston USA
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Presentation] 医工連携による実用的肝グラフト構築を目指して (2015)
  • Author(s): 山下洋市他7名
  • Organizer: 第51回九大生体材料・力学研究会
  • Place of Presentation: 九州大学西新プラザ 福岡
  • Year and Date: 2015-07-28
• [Presentation] 「肝胆膵外科における医工連携の未来」 (2013)
  • Author(s): 山下 洋市、調 憲、米満 吉和、白木川 奈菜、井嶋 博之、前原 喜彦など
  • Organizer: 化学工学会第45回秋期大会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] 「肝胆膵外科における医工連携の未来」 (2013)
  • Author(s): 山下 洋市、調 憲、米満 吉和、白木川 奈菜、井嶋 博之、前原 喜彦など
  • Organizer: INCHEM TOKYO 2013 産学官マッチングフォーラム
  • Place of Presentation: 東京
  • Invited