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In vivo reconstruction of iPS cell-derived human three dimensional hepatic tissue including neural network

Research Project

Project/Area Number 18H02874
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionYokohama City University

Principal Investigator

KOIKE Naoto  横浜市立大学, 医学研究科, 客員教授 (50301081)

Co-Investigator(Kenkyū-buntansha) 田所 友美  横浜市立大学, 医学部, 助教 (20507644)
谷口 英樹  東京大学, 医科学研究所, 教授 (70292555)
武部 貴則  横浜市立大学, 先端医科学研究センター, 教授 (20612625)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords高次肝組織 / 神経系 / 門脈域 / iPS / 再生医療 / iPS細胞
Outline of Final Research Achievements

The hepatic nerve fiver was observed to infiltrate into the liver from porta hepatis just before birth under histological examination using pre and postnatal mouse liver. And we speculated the intrahepatic nerve system play important roles in the maintenance of morphogenesis of the portal area of the liver. Therefore, the liver buds prepared from human iPS cell (iPSC)-derived hepatic progenitor cells, vascular endothelial cells, and mesenchymal stem cell, were cultured on nerve fibers obtained from three-dimensional culture of iPSC derived nerve progenitor cells in order to regenerate a micro-hepatic tissue having a portal area consisting of bile ducts, vessels and nerves. In the result, portal area like morphology (CK19-positive biliary epithelial cells formed bile ductal processes accompanied by nerves and blood vessels) were observed in the liver bud. The liver bud was implanted into the cranial window of the mouse and the process of development was observed under the microscope.

Academic Significance and Societal Importance of the Research Achievements

肝内の自律神経は糖代謝、サーカジアンリズム、食欲に関与するほか、肝血流や肝再生に関与しているとも言われている。しかし、神経系の肝発生に関する意義ははっきりしていない。今回の研究で神経線維が肝内門脈域構築やその形態維持に関与している可能性を示唆する新たな知見を得ることができた。今回の方法でできた神経線維を有する高次肝組織が生体内で成熟し長期安定化できれば、本技術は肝疾患に対する再生医療に利用可能であり、本研究の究極の目的である絶対的に不足している移植臓器に取って代わる革新的な医療技術となりうると思われる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (6 results)

All 2021 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models2021

    • Author(s)
      Mori A, Murata S, Tashiro N, Tadokoro T, Okamoto S, Otsuka R, Wada H, Murata T, Takahashi T, Seino KI, Taniguchi H.
    • Journal Title

      Cells

      Volume: 10 Issue: 2 Pages: 476-476

    • DOI

      10.3390/cells10020476

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【幹細胞治療と疾患】総論 幹細胞治療の課題は克服できるのか?2020

    • Author(s)
      谷口英樹
    • Journal Title

      BIO Clinica

      Volume: 35 Pages: 400-401

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] The Role of Stem Cells in the Hepatobiliary System and in Cancer Development: a Surgeon’s Perspective2018

    • Author(s)
      Naoto Koike
    • Journal Title

      Stem Cells and Cancer in Hepatology

      Volume: なし Pages: 211-253

    • DOI

      10.1016/b978-0-12-812301-0.00011-6

    • ISBN
      9780128123010
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of the hepatic nervous system in the ontogeny of mouse liver2020

    • Author(s)
      Koike Naoto, Tadokoro Tomomi, Murata Soichiro, Sekine Keisuke, Ueno Yasuharu, Okamoto Satoshi, Uchida Yutaro, Takahara Ako, Nanjo Kazuki, Taniguchi Hideki
    • Organizer
      Asian Pacific Association for the Study of the Liver 2020
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 消化器外科医として、臓器再生医療に臨むー生体内で長期機能を有する微小肝組織の開発2019

    • Author(s)
      小池直人
    • Organizer
      札幌医大スキー部創部60周年記念総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 消化器外科医として、臓器再生医療に臨むー生体内で長期機能を有する微小肝組織の開発2019

    • Author(s)
      小池直人
    • Organizer
      札幌医科大学東京同窓会例会
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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