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Development for recellularized liver graft derived from decellularized liver matrix in porcine model

Research Project

Project/Area Number 15K10066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionDokkyo Medical University (2018)
Jichi Medical University (2015-2017)

Principal Investigator

Urahashi Taizen  獨協医科大学, 医学部, 准教授 (90277161)

Co-Investigator(Kenkyū-buntansha) 笠原 尚哉  自治医科大学, 医学部, 助教 (50382891)
寺谷 工  自治医科大学, 医学部, 講師 (70373404)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords臓器移植 / 再生医療 / 脱細胞化臓器 / 臓器再生 / 大動物実験
Outline of Final Research Achievements

We report the results of a pilot study aimed at developing a human-scale whole implantable porcine liver by transplanting recellularized liver graft derived from decellularized liver matrix. Porcine livers were decellularized and the so-obtained liver scaffolds were processed to investigate the vascular patency, degree of decellularization, and scaffold biocompatibility in vitro. Whole liver scaffolds with re-seeding using hepatocytes, endothelial cells and so on were implanted in porcine to assess whether these constructs would determine their biocompatibility in vivo. The explanted recellularized liver scaffolds showed maintenance of these cells engrafted in their putative native locations within the decellularized organ and displayed a liver-like tissue in vivo. Our study shows that whole-organ liver decellularization is possible with maintenance of structure suitable to support recellularized liver tissue for a significant advancement in the bioengineering of whole organs.

Academic Significance and Societal Importance of the Research Achievements

臓器移植は、臓器不全に対する有効な治療法であるが、ドナー臓器の供給不足や拒絶反応も含めた様々な合併症が避けて通れない状況が続いている。近年発展を遂げている再生医療分野でも、未だ細胞・組織単位での応用が検討されている段階である。細胞から臓器単位への再生に飛躍させるためには、足場環境を「臓器単位」で確保する必要があり、本研究のような理想的な足場環境である脱細胞化技術の開発意義は大きいと思われた。また実際にヒトへの応用可能な再生臓器作出を実現させるために、臓器単位での肝再組織化を目指した本研究の成果は意義であるものであり、これを継続・発展させることが必要と考えられた。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2016 2015

All Presentation (3 results) Patent(Industrial Property Rights) (1 results)

  • [Presentation] 脱細胞化臓器を用いた移植可能な再生臓器技術の展望 「再肝臓化」した肝および腎グラフトの開発を中心に2016

    • Author(s)
      浦橋泰然、笠原尚哉、寺谷工
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 「腎臓を肝臓化する試み」ブタ臓器脱細胞化技術を用いた肝細胞充填腎グラフトの開発2016

    • Author(s)
      浦橋泰然、笠原尚哉、寺谷工
    • 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)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 脱細胞化臓器は別機能を持った新たな臓器と変わり得るか?ブタ臓器脱細胞化技術を用いた肝細胞充填肝グラフトおよび腎グラフトの開発2015

    • Author(s)
      浦橋泰然、笠原尚哉、寺谷工
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋国際会議場(名古屋)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 脱細胞プロトコールと組織液2016

    • Inventor(s)
      浦橋泰然
    • Industrial Property Rights Holder
      浦橋泰然
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-03-18
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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