The study for the proliferation mechanism of functional hepatocyte to address the impaired liver regeneration syndrome

• Project/Area Number: 16K09370
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Iwate Medical University
• Principal Investigator: Takikawa Yasuhiro 岩手医科大学, 医学部, 教授 (50254751)
• Research Collaborator: Wang Ting ; Kakisaka Keisuke ; Suzuki Yuji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 急性肝不全 / 肝再生不全 / サイトカイン / 細胆管反応 / 肝細胞 / IL-8 / 肝前駆細胞 / 肝再生 / 胆管細胞 / 偽胆管

Outline of Final Research Achievements

Hepatocyte-cholangiocyte biphenotypic liver progenitor cell populations appear under the impaired liver regeneration syndrome follwing severe liver injury. IL-8 was determined to be one of the responsible factors for inhibiting hepatocyte proliferation and promoting progenitor cell proliferation. These findings suggest that IL-8 is an import target molecule of a purification using artificial liver support for the patients with acute liver failure.

Academic Significance and Societal Importance of the Research Achievements

急性肝不全は肝疾患の中で最も重篤な疾患で、急激な経過をたどる予後不良の疾患であり、専門施設での集中治療、人工肝補助治療あるいは肝移植など極めて高額な治療を必要とする。その理由は、急激かつ広汎な肝細胞死と肝再生不全にある。人工肝補助が発達し、高率に昏睡からの覚醒が得られるようになった現在、内科的救命に向けての最大の障壁は肝再生不全である。本研究は急性肝不全において肝再生不全を引き起こしている物質の候補の一つとしてIL-8を同定し、血液浄化療法の標的分子のとして位置づけることができた。将来の血液浄化療法の開発に重要な情報を与えると考える。

Research Products

• [Journal Article] Liver Regeneration Supported by Muse Cells. (2018)
  • Author(s): Nishizuka SS, Suzuki Y, Katagiri H, Takikawa Y.
  • Journal Title: Adv Exp Med Biol. Volume: 1103 Pages: 219-241
  • DOI: 10.1007/978-4-431-56847-6_12
  • ISBN: 9784431568452, 9784431568476
  • Peer Reviewed
• [Journal Article] A predictive formula of coma onset and prothrombin time to distinguish patients who recover from acute liver injury. (2018)
  • Author(s): Kakisaka K, Suzuki Y, Kataoka K, Okada Y, Miyamoto Y, Kuroda H, Takikawa Y.
  • Journal Title: J Gastroenterol Hepatol Volume: 52 Pages: 277-282
  • NAID: 120006313049
  • Peer Reviewed / Open Access
• [Journal Article] Serum markers for mitochondrial dysfunction and cell death are possible predictive indicators for drug-induced liver injury by direct acting antivirals. (2018)
  • Author(s): Kakisaka K, Yoshida Y, Suzuki Y, Sato T, Kuroda H, Miyasaka A, Takikawa Y
  • Journal Title: Hepatol Res Volume: 48 Pages: 78-86
  • NAID: 120006313048
  • Peer Reviewed / Open Access
• [Journal Article] Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure (2017)
  • Author(s): Kakisaka K, Kataoka K, Suzuki, Y, Kuroda H, Takikawa Y.
  • Journal Title: J Gastroenterol Volume: 52 Pages: 977-985
  • NAID: 120006313047
  • Peer Reviewed / Open Access
• [Journal Article] Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure. (2017)
  • Author(s): 82.Kakisaka K, Kataoka K, Suzuki, Y, Kuroda H, Takikawa Y.
  • Journal Title: Hepatol Res Volume: -
  • NAID: 120006313047
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ductular reactions in the liver regeneration process with local inflammation after physical partial hepatectomy. (2016)
  • Author(s): Suzuki Y, Katagiri H, Wang T, Kakisaka K, Kume K, Nishizuka SS, Takikawa Y.
  • Journal Title: Lab Invest. Volume: 96 Issue: 11 Pages: 1211-22
  • DOI: 10.1038/labinvest.2016.97
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] IL-8 induces transdifferentiation of mature hepatocytes toward the cholangiocyte phenotype. (2018)
  • Author(s): Sasaki T, Suzuki Y, Kakisaka K, Wang T, Takikawa Y.
  • Organizer: International Society for Stem Cell Research Annual Meeting 2018
  • Int'l Joint Research
• [Presentation] 急性肝障害における薬物性肝障害の重症度評価の問題について (2017)
  • Author(s): 柿坂啓介, 宮本康弘, 滝川康裕
  • Organizer: 第53回日本肝臓学会総会
• [Presentation] Technetium-99m-GSA Scintigraphy Obtained Within Three Days of Admission as an Early Predictor of Outcome in Acute Liver Failure and Severe Acute Hepatitis. (2017)
  • Author(s): Suzuki Y, Kakisaka K, Sato T, Mikami R, Takikawa Y.
  • Organizer: The 68th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
• [Presentation] Liver stem/progenitor cells in the mouse liver regeneration process with local inflammation after a physical hepatectomy. (2016)
  • Author(s): 12.Suzuki Y, Katagiri H, Wang T, Kakisaka K, Kume K, Nishizuka S, Takiksawa Y.
  • Organizer: ISSCR 2016 Annual Meeting
  • Place of Presentation: San Francisco.CA,USA
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Book] Muse cells: A New Era of Pluripotent Stem Cells (2018)
  • Author(s): Nishizuka S, Katagiri K, Suzuki Y, and Takikawa Y.
  • Total Pages: 22
  • Publisher: Springer