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Preclinical study on organ preconditioning before transplantation for marginal grafts

Research Project

Project/Area Number 19K09722
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionFujita Health University

Principal Investigator

Kusaka Mamoru  藤田医科大学, 医学部, 教授 (40309141)

Co-Investigator(Kenkyū-buntansha) 佐原 寿史  鹿児島大学, 総合科学域総合研究学系, 准教授 (90452333)
関島 光裕  鹿児島大学, 医用ミニブタ・先端医療開発研究センター, 特任助教 (20568589)
山田 和彦  鹿児島大学, 総合科学域総合研究学系, 教授 (40241103)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腎移植 / 虚血再灌流障害 / マージナルドナー / 灌流保存 / 移植・再生医療 / 臓器保護 / 前臨床実験 / ミニブタ
Outline of Research at the Start

脳死/心停止マージナル腎に適した新たな灌流保存法の確立を目指す前臨床研究として、至適灌流条件を、灌流中と移植後腎機能の相関を基に、温度、酸素化、灌流圧等に焦点をあて検討する。マージナル腎におけるdeath signalの複合的解明を目指し、誘導・放出されるサイトカインを始めとする分泌タンパクやmRNA、バイオマーカーとしての確立が期待される遺伝子発現制御因子miRNAについて、灌流液や血液、尿・移植腎検体、生体内情報伝達物質のエクソソームを用いて解析する。

Outline of Final Research Achievements

The shortage of donor organ is severe, and there is a need to expand the use of marginal kidneys. In this study, we focused on a preservation method (machine perfusion) that enables evaluation and repair of marginal kidneys and investigated the optimal perfusion method and the identification of death signals involved in the development of renal damage. The analysis of clinical specimens showed that total cell free DNA is useful as a death signal in marginal renal transplantation, and large animal experiments suggested that hypothermic machine perfusion can be used to evaluate renal function during preservation and to provide treatment based on death signal control.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、臨床腎移植検体を用いた解析と、遺伝的背景が判明した主要組織適合性抗原MHC確立大動物であるクラウン系ミニブタを用いた実践的橋渡し研究に基づく結果であり、前臨床研究から臨床応用まで一貫した検討を多角的な解析によって得た結果である。従って移植成績向上を目指す橋渡し研究として学術的意義は高く、またマージナルドナー提供推進につながる社会的意義の高い成果であると考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 2019 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Combined α-methylacyl-CoA racemase inhibition and docetaxel treatment reduce cell proliferation and decrease expression of heat shock protein 27 in androgen receptor-variant-7?positive prostate cancer cells2021

    • Author(s)
      Yoshizawa Atsuhiko、Takahara Kiyoshi、Saruta Masanobu、Zennami Kenji、Nukaya Takuhisa、Fukaya Kosuke、Ichino Manabu、Fukami Naohiko、Niimi Atsuko、Sasaki Hitomi、Kusaka Mamoru、Suzuki Motoshi、Sumitomo Makoto、Shiroki Ryoichi
    • Journal Title

      Prostate International

      Volume: 9 Issue: 1 Pages: 18-24

    • DOI

      10.1016/j.prnil.2020.07.001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two cycles of neoadjuvant chemotherapy improves survival in patients with high‐risk upper tract urothelial carcinoma2020

    • Author(s)
      Zennami Kenji、Sumitomo Makoto、Takahara Kiyoshi、Nukaya Takuhisa、Takenaka Masashi、Fukaya Kosuke、Ichino Manabu、Fukami Naohiko、Sasaki Hitomi、Kusaka Mamoru、Shiroki Ryoichi
    • Journal Title

      BJU International

      Volume: 127 Issue: 3 Pages: 332-339

    • DOI

      10.1111/bju.15230

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep learning using preoperative magnetic resonance imaging information to predict early recovery of urinary continence after robot‐assisted radical prostatectomy2020

    • Author(s)
      Sumitomo Makoto、Teramoto Atsushi、Toda Ryo、Fukami Naohiko、Fukaya Kosuke、Zennami Kenji、Ichino Manabu、Takahara Kiyoshi、Kusaka Mamoru、Shiroki Ryoichi
    • Journal Title

      International Journal of Urology

      Volume: 27 Issue: 10 Pages: 922-928

    • DOI

      10.1111/iju.14325

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urodynamic 4D-CT evaluation: 320-row area detector CT scanner combined with PhyZiodynamics software analysis provides an innovative system to evaluate urinary flow and outlet obstructions.2020

    • Author(s)
      Mori S, Yashiro H, Inoue M, Takahara K, Kusaka M, Shiroki R.
    • Journal Title

      Acta Radiol.

      Volume: 61 Issue: 4 Pages: 558-567

    • DOI

      10.1177/0284185119868909

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intra-bone bone marrow transplantation from hCD47 transgenic pigs to baboons prolongs chimerism to >60 days and promotes increased porcine lung transplant survival.2020

    • Author(s)
      Watanabe H, Ariyoshi Y, Pomposelli T, Takeuchi K, Ekanayake-Alper DK, Boyd LK, Arn SJ, Sahara H, Shimizu A, Ayares D, Lorber MI, Sykes M, Sachs DH, Yamada K.
    • Journal Title

      Xenotransplantation.

      Volume: 27 Issue: 1

    • DOI

      10.1111/xen.12552

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical and oncological outcomes of robot-assisted radical prostatectomy with nerve sparing vs. non-nerve sparing for high-risk prostate cancer cases.2019

    • Author(s)
      Takahara K, Sumitomo M, Fukaya K, Jyoudai T, Nishino M, Hikichi M, Zennami K, Nukaya T, Ichino M, Fukami N, Sasaki H, Kusaka M, Shiroki R.
    • Journal Title

      Oncol Lett.

      Volume: 18 Pages: 3896-3902

    • DOI

      10.3892/ol.2019.10692

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation of hybrid porcine thymus containing non-human primate thymic epithelial cells in miniature swine.2019

    • Author(s)
      Sekijima M, Sahara H, Shimizu A, Iwanaga T, Murokawa T, Ariyoshi Y, Pomposelli T, Khosravi Maharlooei M, Sykes M, Yamada K.
    • Journal Title

      Xenotransplantation.

      Volume: 26 Issue: 6

    • DOI

      10.1111/xen.12543

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 高度温虚血腎移植に対する22℃臓器保存の有効性-MHC確立クラウン系ミニブタを用いた体外機械灌流および腎移植モデルによる評価.2021

    • Author(s)
      有吉勇一, 関島光裕, 河合彰浩, 岩永健裕,市成ゆりか, 清水 章, 日下 守, 山田和彦, 佐原寿史
    • Organizer
      第47回日本臓器保存生物医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] TOTAL CELL-FREE DNA AS A NONINVASIVE BIOMAKER OF A DELAYED GRAFT FUNCTION AFTER KIDNEY TRANSPLANTATION FROM DONATION AFTER CARDIAC DEATH2019

    • Author(s)
      Mamoru Kusaka, Hitomi Sasaki, Naohiko Fukami, Kiyoshi Takahara, Manabu Ichino, Taihei Itoh, Takashi Kenmochi, Makoto Sumitomo, Ryoichi Shiroki
    • Organizer
      The European Society for Organ Transplantation (ESOT) Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 鹿児島大学大学院医歯学総合研究科 大動物研究推進部門/医用ミニブタ・先端医療開発共同研究部門

    • URL

      https://sharedspace.sakura.ne.jp/xenotx/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 鹿児島大学医用ミニブタ・先進医療開発研究センター 臓器置換・異種移植外科分野

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~xenotx/index.html

    • Related Report
      2020 Research-status Report 2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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