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Improvement of survival rate and ECM analysis using bio-engineered liver derived 3D scaffold

Research Project

Project/Area Number 18K08701
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionKyoto University

Principal Investigator

Fukumitsu Ken  京都大学, 医学研究科, 特定病院助教 (70700516)

Co-Investigator(Kenkyū-buntansha) 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)
河合 隆之  京都大学, 医学研究科, 客員研究員 (00813867)
小木曾 聡  京都大学, 医学研究科, 助教 (10804734)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脱細胞化 / 細胞外基質 / 胆管上皮細胞 / 臓器作製 / 人工肝臓 / 再生医療 / 人工臓器
Outline of Final Research Achievements

We established a method for circulating rat blood by using decellularized tissue prepared from rat liver to allow cells to attach and grow inside (recellularization). And using this culture system, we developed a method to circulate rat blood into the decellularized liver and a new polymer with anti-platelet activity. In addition, we developed the reconstruction system of bile duct. By using organoids harvested and cultured from livers, we were able to secure the necessary amount of bile duct epithelial cells when needed. This made it technically possible to reduce thrombus formation during blood perfusion and reconstruct bile ducts, which had been difficult in the past in the fabrication of bio-artificial livers.

Academic Significance and Societal Importance of the Research Achievements

臓器不全に対する移植医療は、依然としてドナー不足という深刻な問題を抱えており、肝不全に対する脳死、生体肝移植が広く行われるようになったにも関わらず、ドナー不足のため多くの患者が待機した状態のままで亡くなっている。移植可能な肝臓をin vitroにおいて人工的に作製することは、肝不全の患者の治療機会の増加となる。また、リスクを背負って生体ドナーとなる方の身体的、心理的負担から解放されることに繋がり、より安全な医療へ貢献することとなる。これまで、解決できなかった2つの課題について、解決策となる研究成果であり、今後は臨床応用に向けてさらに発展させていかなければならない。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (45 results)

All 2021 2020 2019 2018 Other

All Journal Article (20 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 3 results) Presentation (22 results) (of which Int'l Joint Research: 5 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Laparoscopic liver resection versus percutaneous radiofrequency ablation for small hepatocellular carcinoma2021

    • Author(s)
      Ogiso Satoshi、Seo Satoru、Eso Yuji、Yoh Tomoaki、Kawai Takayuki、Okumura Shinya、Ishii Takamichi、Fukumitsu Ken、Taura Kojiro、Seno Hiroshi、Uemoto Shinji
    • Journal Title

      HPB

      Volume: 23 Issue: 4 Pages: 533-537

    • DOI

      10.1016/j.hpb.2020.08.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells2020

    • Author(s)
      Takeishi Kazuki、Collin de l’Hortet Alexandra、Wang Yang、Handa Kan、Mashimo Tomoji、Fox Ira J.、Soto-Gutierrez Alejandro
    • Journal Title

      Cell Reports

      Volume: 31 Issue: 9 Pages: 107711-107711

    • DOI

      10.1016/j.celrep.2020.107711

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma2020

    • Author(s)
      Ishii Takamichi、Ito Takashi、Sumiyoshi Shinji、Ogiso Satoshi、Fukumitsu Ken、Seo Satoru、Taura Kojiro、Uemoto Shinji
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 18 Issue: 1 Pages: 319-319

    • DOI

      10.1186/s12957-020-02099-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative assessment of microvascular invasion in hepatocellular carcinoma using preoperative serological and imaging markers2020

    • Author(s)
      Yoh Tomoaki、Seo Satoru、Ogiso Satoshi、Morino Koshiro、Fukumitsu Ken、Ishii Takamichi、Nakamoto Yuji、Taura Kojiro
    • Journal Title

      HPB

      Volume: 20 Issue: 7 Pages: 31224-7

    • DOI

      10.1016/j.hpb.2020.10.024

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transfissural Approach for Laparoscopic Resection of a Deep Segment 8 Lesion in Contact with the Hepatocaval Confluence2020

    • Author(s)
      Ogiso Satoshi、Seo Satoru、Ishii Takamichi、Yoh Tomoaki、Koyama Yukinori、Fukumitsu Ken、Taura Kojiro
    • Journal Title

      Annals of Surgical Oncology

      Volume: 9 Issue: 6 Pages: 09309-09309

    • DOI

      10.1245/s10434-020-09309-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Utility of Mac‐2 Binding Protein Glycosylation Isomer to Evaluate Graft Status After Liver Transplantation2020

    • Author(s)
      Kimura Yusuke、Taura Kojiro、Hai Nam Nguyen、Uemoto Yusuke、Yoshino Kenji、Ikeno Yoshinobu、Okuda Yukihiro、Nishio Takahiro、Yamamoto Gen、Tanabe Kazutaka、Koyama Yukinori、Anazawa Takayuki、Fukumitsu Ken、Ito Takashi、Yagi Shintaro、Kamo Naoko、Seo Satoru、Iwaisako Keiko、Hata Koichiro、Imai Takumi、Uemoto Shinji
    • Journal Title

      Liver Transplantation

      Volume: 27 Issue: 3 Pages: 403-415

    • DOI

      10.1002/lt.25870

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extent of liver resection is associated with incomplete liver restoration and splenomegaly a long period after liver resection2020

    • Author(s)
      Nam Nguyen Hai、Taura Kojiro、Kimura Yusuke、Uemoto Yusuke、Yoshino Kenji、Fukumitsu Ken、Ishii Takamichi、Seo Satoru、Iwaisako Keiko、Uemoto Shinji
    • Journal Title

      Surgery

      Volume: 168 Issue: 1 Pages: 40-48

    • DOI

      10.1016/j.surg.2020.02.022

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation for combined hepatocellular-cholangiocarcinoma: A case series of four patients2020

    • Author(s)
      Ito Takashi、Ishii Takamichi、Sumiyoshi Shinji、Ogiso Satoshi、Fukumitsu Ken、Ito Takashi、Yagi Shintaro、Seo Satoru、Hata Koichiro、Taura Kojiro、Uemoto Shinji
    • Journal Title

      International Journal of Surgery Case Reports

      Volume: 74 Pages: 46-52

    • DOI

      10.1016/j.ijscr.2020.07.069

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] What is a precise anatomic resection of the liver? Proposal of a new evaluation method in the era of fluorescence navigation surgery2020

    • Author(s)
      Nishino Hiroto、Seo Satoru、Hatano Etsuro、Nitta Takashi、Morino Koshiro、Toda Rei、Fukumitsu Ken、Ishii Takamichi、Taura Kojiro、Uemoto Shinji
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Sciences

      Volume: 8 Issue: 6 Pages: 824-824

    • DOI

      10.1002/jhbp.824

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Living donor liver transplantation in situs inversus totalis with a patient‐specific three‐dimensional printed liver model2020

    • Author(s)
      Ishii Takamichi、Fukumitsu Ken、Ogawa Eri、Okamoto Tatsuya、Uemoto Shinji
    • Journal Title

      Pediatric Transplantation

      Volume: 24 Issue: 3 Pages: 13675-13675

    • DOI

      10.1111/petr.13675

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Middle Hepatic Vein Branch-Guided Approach for Laparoscopic Resection of Liver Segment 8 Is Simple, Reliable, and Reproducible2020

    • Author(s)
      Ogiso Satoshi、Seo Satoru、Ishii Takamichi、Anazawa Takayuki、Nagai Kazuyuki、Uchida Yoichiro、Fukumitsu Ken、Ito Takashi、Yagi Shintaro、Kamo Naoko、Hata Koichiro、Masui Toshihiko、Taura Kojiro
    • Journal Title

      Annals of Surgical Oncology

      Volume: 27 Issue: 13 Pages: 5195-5195

    • DOI

      10.1245/s10434-020-08652-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evans Syndrome After Successful Immunosuppressant-Free Living-Donor Liver Transplant2020

    • Author(s)
      Badawy Amr、Kaido Toshimi、Atsushi Yoshizawa、Yagi Shintaro、Hata Koichiro、Kamo Naoko、Fukumitsu Ken、Okajima Hideaki、Uemoto Shinji
    • Journal Title

      Experimental and Clinical Transplantation

      Volume: 18 Issue: 2 Pages: 258-260

    • DOI

      10.6002/ect.2018.0005

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proposed Definition for Oligometastatic Recurrence in Biliary Tract Cancer Based on Results of Locoregional Treatment: A Propensity-Score-Stratified Analysis2020

    • Author(s)
      Morino Koshiro、Seo Satoru、Yoh Tomoaki、Fukumitsu Ken、Ishii Takamichi、Taura Kojiro、Morita Satoshi、Kaido Toshimi、Uemoto Shinji
    • Journal Title

      Annals of Surgical Oncology

      Volume: 27 Issue: 6 Pages: 1908-1917

    • DOI

      10.1245/s10434-020-08207-0

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pretransplantation splenomegaly frequently persists after liver transplantation and can manifest as hypersplenism and graft fibrosis ‐ a retrospective study2020

    • Author(s)
      Nam Nguyen Hai、Taura Kojiro、Yao Siyuan、Kaido Toshimi、Uemoto Yusuke、Kimura Yusuke、Anazawa Takayuki、Fukumitsu Ken、Ito Takashi、Yagi Shintaro、Kamo Naoko、Hata Koichiro、Uemoto Shinji
    • Journal Title

      Transplant International

      Volume: 33 Issue: 12 Pages: 1807-1820

    • DOI

      10.1111/tri.13761

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver Transection-First Approach in Hepatopancreatoduodenectomy for Hilar Cholangiocarcinoma: A Safe and Secure Technique for the Early Assessment of Curable Resection and Vascular Reconstruction2020

    • Author(s)
      Ishii Takamichi、Seo Satoru、Ito Takashi、Ogiso Satoshi、Fukumitsu Ken、Masui Toshihiko、Taura Kojiro
    • Journal Title

      Annals of Surgical Oncology

      Volume: 9 Issue: 6 Pages: 09303-09303

    • DOI

      10.1245/s10434-020-09303-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 生体に移植可能な臓器作製~ドナー不足解消に向けて~2019

    • Author(s)
      福光剣
    • Journal Title

      月刊細胞

      Volume: 51 Pages: 204-207

    • Related Report
      2019 Research-status Report
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 生体に移植可能な臓器作製~ドナー不足解消に向けて~2019

    • Author(s)
      福光剣
    • Journal Title

      細胞

      Volume: 51 Pages: 204-207

    • Related Report
      2018 Research-status Report
  • [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 Research-status Report
    • Peer Reviewed
  • [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 Research-status Report
    • Peer Reviewed
  • [Presentation] 脱細胞化技術と抗血栓ポリマーを用いた血液灌流・移植可能な人工肝臓構築の試み2020

    • Author(s)
      大島 侑, 石井隆道,福光 剣,小木曾 聡,若間聡史, 友藤克博,伊藤 孝,川本浩史,南 貴人,石原一彦, 上本伸二
    • Organizer
      異種移植研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 細胞移植から臓器作製へ2020

    • Author(s)
      福光剣、石井隆道、小木曾聡、安近健太郎、大島侑、川本浩史、南貴人、宮内雄也、小島秀信、岡本晋弥、岡島英明、海道利実、上本伸二
    • Organizer
      日本肝移植学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The three-dimensional cuntom-made liver model for the contribution to the surgical safety2019

    • Author(s)
      福光剣
    • Organizer
      The 6th Kansai-Yeungnam HBP Surgeons Joint Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 再生医学と組織工学に基づく移植ドナー不足解消への試み2019

    • Author(s)
      福光剣
    • Organizer
      日本外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Proposal of a new criterion for the resection of hepatocellular carcinoma: the ALPlat criterion2019

    • Author(s)
      福光剣
    • Organizer
      日本肝胆膵外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 生体肝移植において腎機能障害が予後に与える影響についての検討2019

    • Author(s)
      福光剣
    • Organizer
      日本消化器外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 再生医療と組織工学に基づく、 ドナー不足解消を目指した細胞移植と臓器作製2019

    • Author(s)
      福光剣
    • Organizer
      日本肝移植学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 細胞移植から臓器作製へ2019

    • Author(s)
      福光剣
    • Organizer
      日本肝移植学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 手術の安全性向上における 3次元肝臓模型の有効性に関する検討2019

    • Author(s)
      福光剣
    • Organizer
      日本臨床外科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 再生医学と組織工学に基づく移植ドナー不足解消への試み2019

    • Author(s)
      福光剣、石井隆道、小木曾聡、安近健太郎、大島侑、川本浩史、南貴人、宮内雄也、小島秀信、岡本晋弥、岡島英明、海道利実、上本伸二
    • Organizer
      日本外科学会総会
    • Related Report
      2018 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report
  • [Presentation] 脱細胞化骨格を用いた肝臓再生の試み2018

    • 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 Research-status 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,
    • Organizer
      第20回日本異種移植研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 当院における生体肝移植ドナーの適格基準2018

    • Author(s)
      福光剣、
    • Organizer
      日本肝移植研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] The significance of mapping biopsy to secure the surgical margin2018

    • Author(s)
      Ken Fukumitsu, Siyuan Yao, Kojiro Taura, Takamichi Ishii, Satoru Seo, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto
    • Organizer
      肝胆膵外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] The problem of custom-made liver model for navigation and our improvement2018

    • Author(s)
      福光剣、石井隆道、南貴人、瀬尾智、田浦康二朗、岡島英明、海道利実、上本伸二
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 当院における維持透析症例の生体肝移植成績2018

    • Author(s)
      福光剣、穴澤貴行、伊藤孝司、八木真太郎、加茂直子、秦浩一郎、山敷宣代、岡島英明、海道利実、上本伸二
    • Organizer
      日本移植学会
    • Related Report
      2018 Research-status Report
  • [Presentation] The three-dimensional cuntom-made liver model for the contribution to the surgical safety2018

    • Author(s)
      Ken Fukumitsu, Takamichi Ishii, Satoshi Ogiso, Takahito Minami, Satoru Seo, Kojiro Taura, Hideaki Okajima, Toshimi Kaido, Shinji Uemoto
    • Organizer
      The 6th Kansai-Yeungnam HBP Surgeons Joint Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of PTPE/TIPE from the point of view of surgical complication2018

    • Author(s)
      Ken Fukumitsu, Takamichi Ishii, Satoru Seo, Kojiro Taura, Hideaki Okajima, Toshimi Kaido, shinji Uemoto
    • Organizer
      13th IHPBA World Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] Precision Medicine2020

    • Author(s)
      澤 芳樹(著者・編集)
    • Total Pages
      100
    • Publisher
      北隆館
    • Related Report
      2020 Annual Research Report
  • [Book] Precision Medicine2020

    • Author(s)
      松山 裕(著者・編集)
    • Total Pages
      96
    • Publisher
      17792-07
    • Related Report
      2020 Annual Research Report
  • [Remarks] 再生・幹細胞研究

    • URL

      http://hbptsurgery.kuhp.kyoto-u.ac.jp/%E8%82%9D%E5%86%8D%E7%94%9F/

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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