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Transplantable liver fabrication in a xenogeneic porcine as in vivo bioreactor

Research Project

Project/Area Number 18H04058
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionShiga University of Medical Science (2020)
Kyoto University (2018-2019)

Principal Investigator

Uemoto Shinji  滋賀医科大学, 医学部, 学長 (40252449)

Co-Investigator(Kenkyū-buntansha) 小林 英司  慶應義塾大学, 医学部(信濃町), 特任教授 (00245044)
羽賀 博典  京都大学, 医学研究科, 教授 (10252462)
伊佐 正  京都大学, 医学研究科, 教授 (20212805)
八木 真太郎  京都大学, 医学研究科, 講師 (60447969)
政野 裕紀  京都大学, 医学研究科, 客員研究員 (50806718)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥44,200,000 (Direct Cost: ¥34,000,000、Indirect Cost: ¥10,200,000)
Fiscal Year 2020: ¥15,860,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥3,660,000)
Fiscal Year 2019: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2018: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Keywords肝移植 / 異種移植 / 肝再生 / in vivo bioreactor / 臓器作成
Outline of Final Research Achievements

Our study showed that after auxiliary liver transplantation, the liver graft from Japanese monkey could survive 7days inside the pig body. Furthermore, we demonstrated that the signs of hyperacute rejection, which is specific in xenotransplantation were almost lacked in monkey to pig liver xenotransplantation within 24-hours after transplantation. This study also showed that donor specific antibodies against monkeys were absent in pigs i.e., the xenotransplantation from monkey to pig is an immunologically concordant combination. This suggests the possibility of the use of pig as an in-vivo bio reactor for liver regeneration.

Academic Significance and Societal Importance of the Research Achievements

ブタやサルといった大動物のレベルで、超急性拒絶反応を生じない、いわゆるconcordantな組み合わせを発見した報告はこれまでになく本研究の新規性の一つである。本研究結果を応用することで、ドナーから取り出した小さな肝グラフトを異種動物である第1レシピエントへ移植し、大きい肝グラフトへと再生させた上で第2レシピエントへ再移植する、つまり異種動物であるブタをin-vivo bioreactorとして利用した肝再生戦略の実用化に向けた研究へとつながることが期待される。

Report

(2 results)
  • 2020 Final Research Report ( PDF )
  • 2018 Annual Research Report

Research Products

(11 results)

All 2019 2018

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 2 results)

  • [Journal Article] Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats2019

    • Author(s)
      Doi Junshi、Fujimoto Yasuhiro、Teratani Takumi、Kasahara Naoya、Maeda Masashi、Tsuruyama Tatsuaki、Iida Taku、Yagi Shintaro、Uemoto Shinji
    • Journal Title

      Eur Surg Res.

      Volume: 60 Pages: 63-73

    • DOI

      10.1159/000497434

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Impact of a Nitric Oxide Synthase Inhibitor (L-NAME) on Ischemia?Reperfusion Injury of Cholestatic Livers by Pringle Maneuver and Liver Resection after Bile Duct Ligation in Rats2019

    • Author(s)
      Iwasaki Junji、Afify Mamdouh、Bleilevens Christian、Klinge Uwe、Weiskirchen Ralf、Steitz Julia、Vogt Michael、Yagi Shintaro、Nagai Kazuyuki、Uemoto Shinji、Tolba Rene H.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Pages: 2114-2114

    • DOI

      10.3390/ijms20092114

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preoperative Visceral Adiposity and Muscularity Predict Poor Outcomes after Hepatectomy for Hepatocellular Carcinoma.2019

    • Author(s)
      Hamaguchi Y, Kaido T, Okumura S, Kobayashi A, Shirai H, Yao S, Yagi S, Kamo N, Seo S, Taura K, Okajima H, Uemoto S.
    • Journal Title

      Liver Cancer

      Volume: 8 Pages: 92-109

    • DOI

      10.1159/000488779

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of imbalanced graft‐to‐spleen volume ratio on outcomes following living donor liver transplantation in an era when simultaneous splenectomy is not typically indicated2019

    • Author(s)
      Yao Siyuan、Kaido Toshimi、Yagi Shintaro、Uozumi Ryuji、Iwamura Sena、Miyachi Yosuke、Shirai Hisaya、Kamo Naoko、Taura Kojiro、Okajima Hideaki、Uemoto Shinji
    • Journal Title

      Am J Transplant

      Volume: 印刷中 Pages: 2783-2794

    • DOI

      10.1111/ajt.15337

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone mineral density correlates with survival after resection of extrahepatic biliary malignancies.2018

    • Author(s)
      Yao S, Kaido T, Okumura S, Iwamura S, Miyachi Y, Shirai H, Kobayashi A, Hamaguchi Y, Kamo N, Uozumi R, Yagi S, Uemoto S.
    • Journal Title

      Clinical Nutrition

      Volume: 37 Pages: 32570-6

    • DOI

      10.1016/j.clnu.2018.12.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Etiologies, risk factors, and outcomes of bacterial cholangitis after living donor liver transplantation.2018

    • Author(s)
      Yao S, Yagi S, Nagao M, Uozumi R, Iida T, Iwamura S, Miyachi Y, Shirai H, Kobayashi A, Okumura S, Hamaguchi Y, Masano Y, Kaido T, Okajima H, Uemoto S.
    • Journal Title

      European Journal of Clinical Microbiology & Infectious Diseases

      Volume: 10 Pages: 1973-1982

    • DOI

      10.1007/s10096-018-3333-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver Transplantation for Intermediate-Stage Hepatocellular Carcinoma2018

    • Author(s)
      Kamo Naoko、Kaido Toshimi、Yagi Shintaro、Okajima Hideaki、Uemoto Shinji
    • Journal Title

      Liver Cancer

      Volume: 7 Pages: 179-189

    • DOI

      10.1159/000487058

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Enteral Nutrition with an Immunomodulating Diet Enriched with Hydrolyzed Whey Peptide on Infection After Liver Transplantation2018

    • Author(s)
      Kamo Naoko、Kaido Toshimi、Hamaguchi Yuhei、Uozumi Ryuji、Okumura Shinya、Kobayashi Atsushi、Shirai Hisaya、Yagi Shintaro、Okajima Hideaki、Uemoto Shinji
    • Journal Title

      World Journal of Surgery

      Volume: 42 Pages: 3715-3725

    • DOI

      10.1007/s00268-018-4680-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is Portal Venous Pressure Modulation Still Indicated for All Recipients in Living Donor Liver Transplantation?2018

    • Author(s)
      Yao Siyuan、Kaido Toshimi、Uozumi Ryuji、Yagi Shintaro、Miyachi Yosuke、Fukumitsu Ken、Anazawa Takayuki、Kamo Naoko、Taura Kojiro、Okajima Hideaki、Uemoto Shinji
    • Journal Title

      Liver Transplantation

      Volume: 24 Pages: 1578-1588

    • DOI

      10.1002/lt.25180

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low Preoperative Platelet Count Predicts Risk of Subclinical Posthepatectomy Liver Failure in Right Lobe Donors for Liver Transplantation2018

    • Author(s)
      Yoshino Kenji、Taura Kojiro、Ikeno Yoshinobu、Okuda Yukihiro、Nishio Takahiro、Yamamoto Gen、Seo Satoru、Yagi Shintaro、Hata Koichiro、Kaido Toshimi、Okajima Hideaki、Uemoto Shinji
    • Journal Title

      Liver Transplantation

      Volume: 24 Pages: 1178-1185

    • DOI

      10.1002/lt.25181

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human leukocyte antigen compatibility and lymphocyte cross-matching play no significant role in the current adult-to-adult living donor liver transplantation2018

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

      Clinical Transplantation

      Volume: 32

    • DOI

      10.1111/ctr.13234

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed

URL: 

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

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