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Development of therapeutic modality for liver failure using hepatocyte-based liver organoid transplantation approach

Research Project

Project/Area Number 16K01355
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionOsaka University

Principal Investigator

OHASHI KAZUO  大阪大学, 薬学研究科, 招へい教授 (40364062)

Co-Investigator(Kenkyū-buntansha) 川端 健二  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 幹細胞制御プロジェクト, プロジェクトリーダー (50356234)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords肝細胞移植 / 肝不全 / 再生医療 / 組織工学 / 臓器作成 / 肝組織工学
Outline of Final Research Achievements

The aim of the present study was to establish a novel approach for liver failure using hepatocyte-based liver micro organoid creation. We have utilized hepatocytes isolated and purified from adult mouse livers. Hepatocytes and non-parenchymal cells were used for liver micro organoidc creation. The organoid was then transplanted into the mouse subcutaneous space, kidney capsule space, omental pauch, or intra-abdominal space and liver functions derived from the implanted organoid were investigated. The investigation revealed that intra-abdominal space is a suitable site for their functional survival. When we transplant the liver micro organic into the mice that subsecuently induced severe acute liver failure, the liver micro organid transplantation was found to provide therapeutic value. From these data, transplantation of hepatocyte-based liver micro organid could be a valuable therapeutic tool for liver failure status.

Academic Significance and Societal Importance of the Research Achievements

肝不全を含む末期肝疾患では、肝臓移植が現存する唯一の治療手段である。臓器移植には、深刻かつおそらく解決され得ないドナー不足の問題、多数の医療関係者の関与が必要なこと、臓器提供における社会的課題などの解決すべき課題が伴っている。これらのことから、新規医療の開発は極めて重要な研究開発テーマである。研究代表者の大橋はこれまでに肝細胞を用いた治療的組織作製において世界初の技術開発を数々行ってきた。本研究では、肝不全という病態に焦点をしぼり、肝細胞を用いた組織体(肝オルガノド)を用いた新しい治療開発が目標である。細胞レベルでの肝臓病治療開発に成功すれば、移植医療とともに医療貢献が極めて大きいものとなる。

Report

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

    (24 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] Induced pluripotent stem cell derivation and ex vivo gene correction using a mucopolysaccharidosis type 1 disease mouse model2019

    • Author(s)
      Miki T, Vazquez L, Yanuaria L, Lopez O, Garcia IM, Ohash K, Rodriguez NS
    • Journal Title

      Stem Cells International

      Volume: 2019 Pages: 6978303-6978303

    • DOI

      10.1155/2019/6978303

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A simple and useful predictive assay for evaluating the quality of isolated hepatocytes for hepatocyte transplantation2019

    • Author(s)
      Matsumura M, Imura T, Inagaki A, Ogasawara H, Fukuoka K , Fathi I, Miyagi S, Ohashi K, Unno M, Kamei T, Satomi S, Goto M
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 6166-6166

    • DOI

      10.1038/s41598-019-42720-x

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adult hepatocytes direct liver organogenesis through non-parenchymal cell recruitment in the kidney.2018

    • Author(s)
      Utoh R, Komori J, Kuge H, Tatsumi K, Yamada M, Hirohashi S, Tsutsumi M, Amanuma T, Yoshioka A, Nakajima Y, Wake K, Okano T, Lagasse E, Ohashi K.
    • Journal Title

      J Hepatol.

      Volume: 68 Issue: 4 Pages: 744-753

    • DOI

      10.1016/j.jhep.2017.12.016

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human iPS cell-based liver-like tissue engineering at extrahepatic sites in mice as a new cell therapy for hemophilia B2018

    • Author(s)
      Okamoto R., Takayama K., Akita N., Nagamoto Y., Hosokawa D., Iizuka S., Sakurai F., Suemizu H., Ohashi K., Mizuguchi H.
    • Journal Title

      Cell Transplant

      Volume: 27 Issue: 2 Pages: 299-309

    • DOI

      10.1177/0963689717751734

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 細胞シート工学を用いた血友病新規治療2017

    • Author(s)
      辰巳公平、大橋一夫
    • Journal Title

      Frontiers in Haemophilia

      Volume: 4 Pages: 19-24

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The optimization of short-term hepatocyte preservation prior to transplantation2017

    • Author(s)
      Kengo Fukuoka, Akiko Inagaki, Yasuhiro Nakamura, Muneyuki Matsumura, Satoru Yoshida, Takehiro Imura, Yasuhiro Igarashi, Shigehito Miyagi, Kazuo Ohashi, Shin Enosawa, Takashi Kamei, Michiaki Unno, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Journal Title

      Transplantation Direct

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 肝細胞移植による血友病治療2017

    • Author(s)
      辰巳公平、大橋一夫
    • Journal Title

      Frontiers in Haemophilia

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure.2016

    • Author(s)
      Nagamoto Y., Takayama K., Ohashi K., Okamoto R., Sakurai F., Tachibana M., Kawabata K., Mizuguchi H.
    • Journal Title

      Jpurnal of Hepatology

      Volume: 64 Issue: 5 Pages: 1068-1075

    • DOI

      10.1016/j.jhep.2016.01.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ギリシャ神話(ゼウスの教え)の再考から読み解く肝臓病治療の未来2019

    • Author(s)
      大橋一夫
    • Organizer
      住吉区医師会講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 臓器幹細胞としての肝細胞がおりなす肝臓創生2018

    • Author(s)
      大橋一夫、鵜頭理恵、辰巳公平、岡野光夫、中島祥介、久下博之、Eric Lagasse、小森淳二
    • Organizer
      第25回肝細胞研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 腎被膜下異所性肝臓における新たな胆汁酸排出経路2018

    • Author(s)
      鵜頭理恵、岡野光夫、大橋一夫
    • Organizer
      第25回肝細胞研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高チロシン血症1型モデルマウスの腎被膜下における肝非実質細胞の動員を伴う肝臓創生2018

    • Author(s)
      鵜頭理恵、小森淳二、Lagasse Eric、大橋一夫
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MCVとRDWから観察された鉄剤投与後の赤血球健康化過程2018

    • Author(s)
      恩田久美子、石井洋治、大橋一夫
    • Organizer
      第62回日本透析医学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 高チロシン血症1型モデルマウスの腎被膜下における肝非実質細胞の動員を伴う肝臓創生2018

    • Author(s)
      鵜頭 理恵、小森 淳二、Lagasse Eric、大橋 一夫
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] MCVとRDWから観察された鉄剤投与後の赤血球健康化過程2017

    • Author(s)
      恩田久美子、石井洋治、大橋一夫
    • Organizer
      第62回日本透析医学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 移植前肝細胞におけるviability評価法としてのADP/ATP assayの有用性に関する検証2017

    • Author(s)
      松村宗幸、猪村武弘、小笠原弘之、福岡健吾、稲垣明子、宮城重人、大橋一夫、海野倫明、亀井尚、里見進、 後藤昌史
    • Organizer
      第44回日本臓器保存学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝細胞移植における新規肝細胞移植前評価法の確立2017

    • Author(s)
      松村宗幸、猪村武弘、福岡健吾、稲垣明子、宮城重人、大橋一夫、大内憲明、里見進、後藤昌史
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝細胞移植におけるグラフト保存法の至適化2016

    • Author(s)
      福岡健吾,松村宗幸,吉田諭,猪村武弘,稲垣明子,五十嵐康宏,宮城重人,大橋一夫,絵野沢伸,大内憲明,里見進,後藤昌史
    • Organizer
      第52回日本移植学会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 東京2016

    • Author(s)
      松村宗幸、 猪村武弘、福岡健吾、稲垣明子、宮城重人、大橋一夫、大内憲明、里見進、後藤昌史
    • Organizer
      第52回日本移植学会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] The investigation on target matrix of collagenase G for achieving tailor-made islet isolation2016

    • Author(s)
      Satoru Yoshida, Youhei Yamagata, Kanako Nakagawa, Kazuhisa Maeda, Kazutaka Murayama, Kimiko Watanabe, Takehiro Imura, Akiko Inagaki, Yasuhiro Igarashi, Shigehito Miyagi, Kazuo Ohashi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Organizer
      26th International Congress of the Transplantation Society
    • Place of Presentation
      Hong Kong
    • Year and Date
      2016-08-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optimization of procedures for short-time hepatocyte preservation prior to transplantation2016

    • Author(s)
      Kengo Fukuoka, Satoru Yoshida, Takehiro Imura, Akiko Inagaki, Yasuhiro Igarashi, Shigehito Miyagi, Kazuo Ohashi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Organizer
      26th International Congress of the Transplantation Society
    • Place of Presentation
      Hong Kong
    • Year and Date
      2016-08-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝細胞がおりなす肝オルガノエンジニアリングと展望2016

    • Author(s)
      大橋一夫、鵜頭理恵、小森淳二、Eric Lagasse、中島祥介
    • 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
    • Year and Date
      2016-04-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 経肝静脈的肝細胞移植法による障害肝中心静脈域(zone3)への領域選択的肝細胞移植の実験的検討2016

    • Author(s)
      山下信吾、大橋一夫、鵜頭理恵、後藤祐一郎、山本雅一
    • 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
    • Year and Date
      2016-04-13
    • Related Report
      2016 Research-status Report
  • [Book] バイオ・医療への3Dプリンティング技術の開発最前線2016

    • Author(s)
      大橋一夫
    • Total Pages
      230
    • Publisher
      シーエムシー・リサーチ
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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