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Engineering of three dimensional human hepatic tissue with microvascular network and bile duct structures

Research Project

Project/Area Number 26293291
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 武部 貴則  横浜市立大学, 医学部, 准教授 (20612625)
谷口 英樹  横浜市立大学, 医学(系)研究科(研究院), 教授 (70292555)
Research Collaborator MURATA Souichirou  横浜市立大学, 医学部, 准教授 (40436275)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords肝再生 / 微小血管 / 胆管構築 / ヒト型高次肝組織 / 胆管 / 血管 / iPS / 再生医学 / 移植・再生医療 / 微小血管網 / 高次肝組織
Outline of Final Research Achievements

We created three-dimensional liver buds in vitro by co-culturing hepatic endoderm cells with endothelial and mesenchymal cells prepared from human iPSC. The liver buds were implanted into mouse cranial windows or intra-abdominal organs and then the microvascular networks and bile duct structures reconstructed in the liver buds were histologically observed. In the results, HNF4a positive hepatic cord like structures and SOX9 positive bile duct structures were observed. The canaliculus like structures were also observed within hepatic cord like structures, however, bile production could not be seen. Whereas EphB4 positive microvessels were observed in these tissues, intralobular veins and arteries could not be identified. We transplanted the human liver buds into the liver of rat cirrhosis models to examine the inhibition effects of liver fibrosis. In the results, human albumin was detected in rat serum, and an improvement of liver fibrosis was confirmed.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (8 results)

All 2017 2016 2015 2014

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Liver Regeneration Using Cultured Liver Bud2017

    • Author(s)
      Sekine K, Takebe T, Taniguchi H.
    • Journal Title

      Methods Mol Biol

      Volume: 1597 Pages: 207-216

    • DOI

      10.1007/978-1-4939-6949-4_15

    • ISBN
      9781493969470, 9781493969494
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nutritional modulation of mouse and human liver bud growth through a branched-chain amino acid metabolism.2017

    • Author(s)
      Koike H, Zhang RR, Ueno Y, Sekine K, Zheng YW, Takebe T, Taniguchi H.
    • Journal Title

      Development

      Volume: 144(6) Pages: 1018-1024

    • DOI

      10.1242/dev.143032

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 【幹細胞研究と再生医療】 iPS細胞の応用技術 iPS細胞を用いたヒト肝臓創出技術の開発2015

    • Author(s)
      谷口英樹、武部貴則
    • Journal Title

      腎と透析

      Volume: 79 Pages: 950-954

    • Related Report
      2015 Annual Research Report
  • [Presentation] 血管化膵島移植による革新的糖尿病治療法の確立2017

    • Author(s)
      高橋禎暢、武部貴則、小池直人、関根圭輔、谷口英樹
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Prognostic value of tumor infiltrating CD8+ T cells and FoxP3+ Treg in HCC patients after surgical treatment2016

    • Author(s)
      Koike N, Ohshima Y., Takeuchi T., Kubota T., Shiraishi T., Arita S.
    • Organizer
      IASGO World Congress 2016
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-09-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血管化膵島移植による革新的糖尿病治療法の確立2016

    • Author(s)
      高橋禎暢、武部貴則、小池直人、関根圭輔、谷口英樹
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市北区)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞を用いた三次元組織作成のための基盤技術2015

    • Author(s)
      谷口英樹
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いたヒト器官原基創出法の開発2014

    • Author(s)
      谷口英樹
    • Organizer
      第35回日本炎症・再生医学会
    • Place of Presentation
      万国津梁館(沖縄県名護市)
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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