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Development of the transplantable artificial liver using iPS cells and decellularized liver

Research Project

Project/Area Number 16H05489
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatric surgery
Research InstitutionKyoto University

Principal Investigator

Yasuchika Kentaro  京都大学, 医学研究科, 客員研究員 (00378895)

Co-Investigator(Kenkyū-buntansha) 河合 隆之  京都大学, 医学研究科, 客員研究員 (00813867)
上本 伸二  京都大学, 医学研究科, 教授 (40252449)
石井 隆道  京都大学, 医学研究科, 特定病院助教 (70456789)
福光 剣  京都大学, 医学研究科, 特定病院助教 (70700516)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords臓器作製 / 幹細胞生物学 / 再生医療 / 多能性幹細胞 / 人工肝臓 / 肝移植 / 組織工学 / 肝臓移植 / ヒトiPS細胞 / 人工臓器 / 再生医学 / iPS細胞 / 脱細胞化肝臓
Outline of Final Research Achievements

We produced a transplantable bio-artificial liver using the decellularized tissue derived from rat native liver. First, we established a protocol and evaluation system such as cell engraftment method and culture method for decellularized tissue of liver and primary culture cells. Next, the basic structure of the liver was reproduced using hepatocyte-like cells differentiated from human iPS cells, and the fundamental hepatocyte function was evaluated. Moreover, not only in the liver but also in the small intestine, a transplantable artificial small intestine was developed using the same method. When decellularized tissue of the rat small intestine was used at the defect site of the small intestine, regeneration of the small intestine wall was observed with the decellularized tissue as a scaffold.

Academic Significance and Societal Importance of the Research Achievements

移植医療において、ドナー不足は深刻な課題である。様々な代替医療の研究が進む中、移植可能な人工肝臓の作製は、課題を解決する方法として、最も理想的な手段であるが実現には多くの困難を伴う方法でもある。脱細胞化組織や自己の組織から作製するiPS細胞を用いることで、移植可能でかつ拒絶反応のない理想的な臓器を作製することが理論的に可能となる。今回、ヒトiPS細胞から肝細胞様細胞へ分化誘導した後に脱細胞化組織の中で培養し、肝臓組織の一部の組織構造や機能を再現したことを示した。今後は、肝不全の患者を救命できるだけの十分な機能と組織構造を有する肝臓を作製できるよう、さらなる技術開発が期待される。

Report

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

    (26 results)

All 2019 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (21 results) (of which Int'l Joint Research: 9 results,  Invited: 2 results)

  • [Journal Article] Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold2019

    • Author(s)
      Takahito Minami, Takamichi Ishii, Kentaro Yasuchika, Ken Fukumitsu, Satoshi Ogiso, Yuya Miyauchi, Hidenobu Kojima, Takayuki Kawai, Ryoya Yamaoka, Yu Oshima, Hiroshi Kawamoto, Maki Kotaka, Katsutaro Yasuda, Kenji Osafune, Shinji Uemoto
    • Journal Title

      Regenerative therapy

      Volume: 10 Pages: 127-133

    • DOI

      10.1016/j.reth.2019.03.002

    • NAID

      120006719314

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis.2018

    • Author(s)
      Yamaoka R, Ishii T, Kawai T, Yasuchika K, Miyauchi Y, Kojima H, Katayama H, Ogiso S, Fukumitsu K, Uemoto S
    • Journal Title

      J Surg Oncol.

      Volume: 4 Issue: 4 Pages: 664-674

    • DOI

      10.1002/jso.25192

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of practical recellularized liver graft for blood perfusion using primary rat hepatocytes and liver sinusoidal endothelial cells2018

    • Author(s)
      Kojima H.、Yasuchika K.、Fukumitsu K.、Ishii T.、Ogiso S.、Miyauchi Y.、Yamaoka R.、Kawai T.、Katayama H.、Yoshitoshi-Uebayashi E. Y.、Kita S.、Yasuda K.、Sasaki N.、Komori J.、Uemoto S.
    • Journal Title

      American Journal of Transplantation

      Volume: 印刷中 Issue: 6 Pages: 1351-13559

    • DOI

      10.1111/ajt.14666

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of non-viral, transgene-free hepatocyte like cells with piggyBac transposon.2017

    • Author(s)
      Katayama H, et.al.
    • Journal Title

      Sci Rep.

      Volume: 15 Issue: 1 Pages: 44498-44498

    • DOI

      10.1038/srep44498

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel three-dimensional culture system maintaining the physiological extracellular matrix of fibrotic model livers accelerates progression of hepatocellular carcinoma cells2017

    • Author(s)
      Miyauchi Yuya、Yasuchika Kentaro、Fukumitsu Ken、Ishii Takamichi、Ogiso Satoshi、Minami Takahito、Kojima Hidenobu、Yamaoka Ryoya、Katayama Hokahiro、Kawai Takayuki、Yoshitoshi-Uebayashi Elena Yukie、Kita Sadahiko、Yasuda Katsutaro、Sasaki Naoya、Uemoto Shinji
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-09391-y

    • NAID

      120006364100

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 脱細胞化骨格を用いた肝臓再生の試み2019

    • Author(s)
      小島秀信、石井隆道、福光 劍、小木曾 聡、友藤克博、伊藤 孝、大島 侑、川本浩史、南 貴人、宮内雄也、上本伸二
    • Organizer
      第21回日本異種移植研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Vascularization of recellularized liver graft2018

    • Author(s)
      Hidenobu Kojima, Takamichi Ishii, Ken Fukumitsu, Yu Oshima, Hiroshi Kawamoto, Takahito Minami, Yuya Miyauchi, Ryoya Yamaoka, Takayuki Kawai, Shinji Uemoto
    • Organizer
      8th International Forum of Liver Surgery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of endothelial cells on the engineered liver recellularized with primary rat hepatocytes2018

    • Author(s)
      Hidenobu Kojima, Takamichi Ishii, Ken Fukumitsu, Yu Oshima, Hiroshi Kawamoto, Takahito Minami, Yuya Miyauchi, Ryoya Yamaoka, Takayuki Kawai, Shinji Uemoto
    • Organizer
      13th IHPBA World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endothelialized liver scaffold-the impact of endothelial cells on recellularized liver-2018

    • Author(s)
      Hidenobu Kojima, Takamichi Ishii, Ken Fukumitsu, Yu Oshima, Hiroshi Kawamoto, Takahito Minami, Yuya Miyauchi, Ryoya Yamaoka, Takayuki Kawai, Shinji Uemoto
    • Organizer
      第30回日本肝胆膵外科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 再細胞化肝臓における内皮化の効果2018

    • Author(s)
      小島秀信、石井隆道、福光 剣、大島 侑、川本浩史、南 貴人、宮内雄也、山岡竜也、河合隆之、上本伸二
    • Organizer
      第54回肝臓学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS由来肝細胞様細胞とラット脱細胞化肝臓骨格を用いた臓器作製2018

    • Author(s)
      南 貴人,宮内 雄也,小島 秀信,大島 侑,川本 浩史,山岡 竜也,河合 隆之,上林 エレーナ 幸江,安田 勝太郎,福光 剣,石井 隆道, 岡島 英明,海道 利実,上本 伸二
    • Organizer
      第20回日本異種移植研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 脱細胞化小腸グラフトを使用した、生体内での小腸再生の試み2018

    • Author(s)
      小島秀信
    • Organizer
      第30回日本小腸移植研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Vascularization of recellularized liver graft2018

    • Author(s)
      Hidenobu Kojima
    • Organizer
      8th International Forum of Liver Surgery
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 再細胞化肝臓における内皮化の効果2018

    • Author(s)
      小島秀信
    • Organizer
      第54回肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Endothelialized liver scaffold-the impact of endothelial cells on recellularized liver-2018

    • Author(s)
      Hidenobu Kojima
    • Organizer
      第30回肝胆膵外科学会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Impact of endothelial cells on the engineered liver recellularized with primary rat hepatocytes2018

    • Author(s)
      Hidenobu Kojima
    • Organizer
      13th IHPBA World Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel culture system preserving natural scaffolds of fibrotic livers accelerates progression of hepatocellular carcinoma cells2018

    • Author(s)
      Yuya Miyauchi, Kentaro Yasuchika Yu Oshima, Hiroshi Kawamoto, Takahito Minami, Hidenobu Kojima, Ryoya Yamaoka, Takayuki Kawai, Satoshi Ogiso, Ken Fukumitsu, Takamichi Ishii, Shinji Uemoto
    • Organizer
      The Asian Pacific Association for the Study of the Liver Single topic Conference on HCC
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞外基質による微小環境は肝細胞癌の不均一性に寄与する2018

    • Author(s)
      宮内雄也 石井隆道 河合隆之 川本浩 大島侑 南貴人 小島秀信 山岡竜也 小木曾聡 福光:剣 岡島英明 海道利実 上本伸二
    • Organizer
      肝癌研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトiPS由来肝細胞様細胞とラット脱細胞化肝臓骨格を用いた臓器作製2018

    • Author(s)
      南 貴人、宮内 雄也、小島 秀信、大島 侑、川本 浩史、山岡 竜也、河合 隆之、上林エレーナ幸江、安田 勝太郎、福光 剣、石井 隆道、上本 伸二
    • Organizer
      第20回日本異種移植研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Approaches to fabricate practical recellularized liver graft using primary liver cells-our seeding method for optimal distribution of parenchymal and endothelial cells-2017

    • Author(s)
      Hidenobu Kojima
    • Organizer
      52nd annual meeting of the European Association for the Study of the Liver (EASL)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Alternative usage of recellularized liver graft as clinical application2017

    • Author(s)
      Hidenobu Kojima
    • Organizer
      15th Transplantation Science Symposium (TSS)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Promising application for drug screening with recellularized whole-liver scaffold2017

    • Author(s)
      Hidenobu Kojima
    • Organizer
      103rd Annual American College of Surgeons (ACS) Clinical Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体への応用を目指した再細胞化肝臓の構築 実質細胞と内皮細胞の再細胞化法2017

    • Author(s)
      小島秀信
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A novel three-dimensional culture system, decellularized-tissue obtained from cirrhotic livers, enhances an epithelial-mesenchymal transition phenotype in HCC cells2017

    • Author(s)
      Yuya Miyauchi, Kentaro Yasuchika, Ken Fukumitsu, Satoshi Ogiso, Hidenobu Kojima, Ryoya Yamaoka, Takayuki Kawai, Hokahiro Katayama, Elena Y Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Naoya Sasaki, Takamichi Ishii, Junji Komori, Shinji Uemoto
    • Organizer
      American college of Surgeons clinical congress
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Optimizing recellularization of decellularized whole-liver graft: from which route and with which cell?2016

    • Author(s)
      Satoshi Ogiso, Kentaro Yasuchika, Ken Fukumitsu, Takamichi Ishii, Hidenobu Kojima, Yuya Miyauchi, Ryoya Yamaoka, Hokahiro Katayama, Takayuki Kawai, Sadahiko Kita, Shinji Uemoto
    • Organizer
      The American College of Surgeons 102nd Clinical Congress
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2016-10-19
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biliary tree as a window for repopulation of the decellularized liver scaffold.2016

    • Author(s)
      Satoshi Ogiso, Kentaro Yasuchika, Ken Fukumitsu, Takamichi Ishii, Hidenobu Kojima, Yuya Miyauchi, Ryoya Yamaoka, Hokahiro Katayama, Takayuki Kawai, Elena Yukie Yoshitoshi, Sadahiko Kita, Katsutaro Yasuda, Shinji Uemoto
    • Organizer
      26th International congress of the transplantation society
    • Place of Presentation
      Hong Kong
    • Year and Date
      2016-08-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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

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