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Development of new therapy for congenital metabolic disorders using functional three-dimensional liver structures constructed by stem cells from human exfoliated deciduous teeth

Research Project

Project/Area Number 24592696
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionKyushu University

Principal Investigator

YANAGI Yusuke  九州大学, 医学(系)研究科(研究院), 研究員 (30596664)

Co-Investigator(Kenkyū-buntansha) TAGUCHI Tomoaki  九州大学, 医学(系)研究科(研究院), 教授 (20197247)
NAKAYAMA Koichi  佐賀大学, 工学(系)研究科(研究院), 教授 (50420609)
HAYASHIDA Makoto  九州大学, 大学病院, 助教 (70452761)
KOHASHI Kenichi  九州大学, 大学病院, 講師 (10529879)
IHARA Kenji  大分大学, 医学(系)研究科(研究院), 教授 (80294932)
Co-Investigator(Renkei-kenkyūsha) YAMAZA Takayoshi  九州大学, 歯学(系)研究科(研究院), 講師 (80304814)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords歯髄幹細胞 / 肝細胞移植 / 肝組織工学 / 代謝性肝疾患 / 人工臓器 / 再生医療 / 再生医学 / 先天性肝疾患 / 乳歯歯髄幹細胞
Outline of Final Research Achievements

We successfully differentiated stem cells from Human Exfoliated Deciduous teeth(SHED) to hepatocyte-like cells by our culture system. SHED derived hepatocyte-like cells(SHED-Hep) showed low immunogenicity and suppression of T cells in vitro. Following these result, we xenografted SHED-Hep into carbon tetrachloride (CCl4)-induced chronic liver fibrosis model mice without immunosuppressive therapy, showing the engraftment in the recipient liver, anti-fibrotic efficacy and prolonged survival. In the next step, we fabricated 3D liver construct with human primary hepatocytes, umbilical vein endothelial cells and mesenchymal stem cells using a bio-3D printer. It’s microstructure resembled real liver tissue in histology, and it showed liver specific functions. We also succeed in biofabrication of 3D liver construct with SHED-Hep. In future, we will transplant this SHED derived construct to develop new liver regenerative therapy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (11 results)

All 2014 2013 2012 Other

All Presentation (10 results) Patent(Industrial Property Rights) (1 results)

  • [Presentation] 四塩化炭素誘導肝硬変モデルマウスに対するヒト脱落乳歯幹細胞移植療法の有効性に関する研究2014

    • Author(s)
      栁 佑典
    • Organizer
      第51回 日本小児外科学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-05-08 – 2014-05-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いた肝組織再構築の試み2013

    • Author(s)
      柳 佑典
    • Organizer
      第113回日本外科学会総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いた立体的肝組織の構築2013

    • Author(s)
      柳 佑典
    • Organizer
      第50回日本小児外科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いた機能的三次元肝構造体の構築2013

    • Author(s)
      栁 佑典
    • Organizer
      第12回 日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いた2013

    • Author(s)
      栁 佑典
    • Organizer
      第113回 日本外科学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いたscaffold free肝臓構造体の構築2012

    • Author(s)
      栁 佑典
    • Organizer
      第11回 日本再生医療学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いた立体的肝細胞構造体の構築2012

    • Author(s)
      栁 佑典
    • Organizer
      第48回日本移植学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Construction of scaffold-free three dimensional liver tissue by spheroid fusion using the bio 3D printer.

    • Author(s)
      Yusuke Yanagi
    • Organizer
      The 24th Fukuoka International Symposium on Pediatric/Maternal-Child Health research
    • Place of Presentation
      Fukuoka
    • Related Report
      2013 Research-status Report
  • [Presentation] スフェロイド自動積層装置を用いたscaffold-free機能的三次元肝組織の構築

    • Author(s)
      柳 佑典
    • Organizer
      第1回細胞凝集研究会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] バイオラピッドプロトタイピングシステム(BRP system)を用いた肝組織再構築の試み

    • Author(s)
      栁 佑典
    • Organizer
      第39回日本胆道閉鎖症研究会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 肝臓機能をもったミニ肝臓構造体2013

    • Inventor(s)
      栁 佑典
    • Industrial Property Rights Holder
      栁 佑典
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2013-056835
    • Filing Date
      2013
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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