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2012 Fiscal Year Final Research Report

Development of a novel organ preservation solution for the use of liver transplantation

Research Project

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Project/Area Number 22249048
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionHokkaido University

Principal Investigator

TODO Satoru  北海道大学, 大学院・医学研究科, 特任教授 (60136463)

Co-Investigator(Kenkyū-buntansha) OZAKI Michitaka  北海道大学, 大学院・医学研究科, 特任教授 (80256510)
FURUKAWA Hiroyuki  旭川医科大学, 大学院・医学研究科, 教授 (70292026)
YAMASHITA Kenichiro  北海道大学, 大学院・医学研究科, 特任准教授 (00399940)
FUKAI Moto  北海道大学, 病院・消化器外科学I, 医員 (60374344)
SUGAWARA Mitsuru  北海道大学, 大学院・薬学研究院, 教授 (60332467)
Co-Investigator(Renkei-kenkyūsha) MATSUSHITA Michiaki  北海道大学, 大学院・保健学研究院, 教授 (20250425)
SHIMAMURA Tsuyoshi  北海道大学, 病院・臓器移植医療部, 准教授 (00333617)
TANIGUCHI Masahiko  旭川医科大学, 大学院・医学研究科, 准教授 (30374333)
SUZUKI Tomomi  北海道大学, 大学院・医学研究科, 特任准教授 (70374238)
Project Period (FY) 2010 – 2012
Keywords移植外科
Research Abstract

We explored the necessary condition of heavy water containing buffer for the use of simple cold preservation. The novel solution appeared to show excellent cytoprotection in various cells, and rat liver and heart, due to the inhibition of cytosolic Ca2+ overload and cytoskeletal breakdown, and stimulation of aerobic respiration. However, these beneficial effects were abolished in liver and kidney preservation and transplantation of dogs, possibly due to the stimulation of intravascular agglutination by PEG. To proceed to the clinical application, customization of PEG concentration should be explored. Further, since the main action of heavy water containing buffer is stimulation of aerobic respiration, we should find better way to provide oxygen without agglutination for the next step.

  • Research Products

    (45 results)

All 2013 2012 2011 2010 Other

All Journal Article (14 results) (of which Peer Reviewed: 11 results) Presentation (30 results) Book (1 results)

  • [Journal Article] Does heavy water attenuate cold preservation and reperfusion injury in canine kidney?2012

    • Author(s)
      Hirokata G, Fukai M, Todo S. et al
    • Journal Title

      Low TemperatureMedicine

      Volume: 38(3) Pages: 62-68

    • Peer Reviewed
  • [Journal Article] Immunosuppressive Effects ofDTCM-G, a Novel Inhibitor of the mTOR Downstream Signaling Pathway2012

    • Author(s)
      Shibasaki S, Yamashita K, Todo S. et al
    • Journal Title

      Transplantation

      Volume: 95(4) Pages: 542-50

    • Peer Reviewed
  • [Journal Article] Long-Term Hepatic Allograft Acceptance Based on CD40 Blockade by ASKP1240 in Nonhuman Primates2012

    • Author(s)
      Oura T, Yamashita K, Todo S. et al
    • Journal Title

      Am JTransplant

      Volume: 12(7) Pages: 1740-54

    • Peer Reviewed
  • [Journal Article] Successful transplan -tation of rat hearts subjected to extended cold preservation with a novel preservationsolution2012

    • Author(s)
      Wakayama K, Fukai M, Todo S.et al
    • Journal Title

      Transpl Int

      Volume: 25(6) Pages: 696-706

    • Peer Reviewed
  • [Journal Article] Immunomodulatory effect of nuclear factor-κB inhibition bydehydroxymethyl -epoxyquinomicin in combination with donor-specific blood transfusion2012

    • Author(s)
      Goto R, Yamashita K, Todo S. et al
    • Journal Title

      Transplantation

      Volume: 93(8) Pages: 777-86

    • Peer Reviewed
  • [Journal Article] Dendritic Cells Conditioned With NK026680 Prolong Cardiac Allograft Survival in Mice2012

    • Author(s)
      Shibasaki S, Yamashita K, Todo S.et al
    • Journal Title

      Transplantation

      Volume: 93(12) Pages: 1229-37

    • Peer Reviewed
  • [Journal Article] 臓器保存の現状と今後--新しい保存法開発のための基礎知識-- (研究の新しい展開)2011

    • Author(s)
      深井原、嶋村剛
    • Journal Title

      医学のあゆみ

      Volume: 237(5) Pages: 583-591

  • [Journal Article] 臓器保存における重水の可能性2011

    • Author(s)
      深井原、藤堂省
    • Journal Title

      Organ Biology

      Volume: 18(1) Pages: 101-107

  • [Journal Article] 臓器移植の非侵襲的モニタリング法の開発2011

    • Author(s)
      尾崎倫孝、深井原、藤堂省、他
    • Journal Title

      Organ Biology

      Volume: 18(1) Pages: 134-140

  • [Journal Article] Anovel NF-κB inhibitor,dehydroxymethyl -epoxyquinomicin, ameliorates inflammatory colonic injury in mice2011

    • Author(s)
      Funakoshi T, Yamashita K, Todo S
    • Journal Title

      J Crohns Colitis

      Volume: 6(2) Pages: 215-25

    • Peer Reviewed
  • [Journal Article] Induction of insulin-dependent diabetes mellitus by total pancreatectomy for pancreatic islet transplantation in cynomolgus monkeys2011

    • Author(s)
      Yoshida T, Suzuki T, Todo S. et al
    • Journal Title

      J Hepatobiliary Pancreat Sci

      Volume: 19(6) Pages: 661-6

    • Peer Reviewed
  • [Journal Article] Liver transplantation for hepatocellular carcinoma: the Japanese experience2010

    • Author(s)
      Furukawa H, Shimamura T, Todo S
    • Journal Title

      Hepatobiliary Pancreat Sci

      Volume: 17(5) Pages: 533-538

    • Peer Reviewed
  • [Journal Article] Three-dimensional computed tomography scan analysis of hepatic vasculatures in the donor liver for living donor liver transplantation2010

    • Author(s)
      Uchida K, Furukawa H, Todo S. et al
    • Journal Title

      Liver Transpl

      Volume: 16(9) Pages: 1062-1068

    • Peer Reviewed
  • [Journal Article] Risk factors for portal vein complications in pediatric living donor liver transplantation2010

    • Author(s)
      Shibasaki S, Furukawa H, Todo S. et al
    • Journal Title

      Clin Transplant

      Volume: 24(4) Pages: 550-556

    • Peer Reviewed
  • [Presentation] Heavy water confers protection against hepatic cold ischemia injury and hydrogen confers protection against hepatic reperfusion injury in isolated perfused rat liver2013

    • Author(s)
      Shimada S, Fukai M, Todo S, et al
    • Organizer
      The American Transplant Congress
    • Place of Presentation
      Seattle, WA, USA; Washington State Convention & Trade Center
    • Year and Date
      20130518-22
  • [Presentation] 低温下でエネルギー産生を賦活化させる新しい方法~有効性と普遍性2013

    • Author(s)
      深井原、藤堂省、他
    • Organizer
      日本外科学
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      20130412-14
  • [Presentation] ラット冷保存肝における再灌流時水素ガス投与の効果2013

    • Author(s)
      島田慎吾、深井原、藤堂省、他
    • Organizer
      日本外科学会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      20130412-14
  • [Presentation] 生体肝移植における門脈圧および門脈血流の術後早期予後に及ぼす影響2013

    • Author(s)
      青柳武史、山下健一郎、藤堂省、他
    • Organizer
      第113回日本外科学会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      20130412-14
  • [Presentation] 臓器保存液の現状と今後の展望2012

    • Author(s)
      深井原、藤堂省,他
    • Organizer
      第39回日本臓器保存生物医学会
    • Place of Presentation
      コラッセ福島
    • Year and Date
      20121116-17
  • [Presentation] ラット冷保存肝における再灌流時水素ガス投与の効果2012

    • Author(s)
      島田慎吾 ,深井原 ,藤堂省 他
    • Organizer
      日本臓器保存生物医学会
    • Place of Presentation
      コラッセ福島
    • Year and Date
      20121116-17
  • [Presentation] 北海道の臓器提供推進モデルの全国展開に向けて2012

    • Author(s)
      藤堂省
    • Organizer
      日本移植学会
    • Place of Presentation
      名古屋;ウィンクあいち
    • Year and Date
      20120920-22
  • [Presentation] 当科における脳死肝移植適応基準2012

    • Author(s)
      大浦哲、藤堂省
    • Organizer
      日本移植学会
    • Place of Presentation
      名古屋;ウィンクあいち
    • Year and Date
      20120920-22
  • [Presentation] マウス肝温虚血再灌流障害における硫化水素の効果2012

    • Author(s)
      島田慎吾、深井原、藤堂省
    • Organizer
      日本移植学会
    • Place of Presentation
      名古屋;ウィンクあいち
    • Year and Date
      20120920-22
  • [Presentation] Hydrogen Sulfide Confers Protection Against Hepatic Warm Ischemia Reperfusion Injury in Mice2012

    • Author(s)
      Shimada S, Fukai M, Todo S. et al
    • Organizer
      XXIV International Congress of The Transplantation Society
    • Place of Presentation
      Berlin, Germany; InternationalCongress Center Berlin
    • Year and Date
      20120715-19
  • [Presentation] 当科における脳死肝移植ドナー適応基準2012

    • Author(s)
      大浦哲、嶋村剛、藤堂省,他
    • Organizer
      第112回日本外科学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      20120412-14
  • [Presentation] マウス肝虚血再灌流モデルにおける硫化水素の肝保護効果2012

    • Author(s)
      島田慎吾、深井原、藤堂省, 他
    • Organizer
      第112回日本外科学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      20120412-14
  • [Presentation] 低温酸素化灌流による臓器修復は可能か?~ミトコンドリア機能と細胞内 Ca^2+2012

    • Author(s)
      深井原、藤堂省, 他
    • Organizer
      第112回日本外科学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      20120412-14
  • [Presentation] 新規臓器保存液(FJ 液)による肝冷凍保存再灌流障害の軽減~FJ 液の重要な成分2011

    • Author(s)
      旭火華、深井原、藤堂省
    • Organizer
      日本外科学会
    • Place of Presentation
      震災;紙上開催
    • Year and Date
      20110526-28
  • [Presentation] 低温下で好気代謝を促進する新規臓器保存液の至的条件~低温酸素化灌流保存法への応用を目指した基礎的検討2011

    • Author(s)
      深井原、若山顕治、藤堂省、他
    • Organizer
      日本外科学会
    • Place of Presentation
      震災;紙上開催
    • Year and Date
      20110526-28
  • [Presentation] ラット心冷保存・移植後のグラフト機能の評価2011

    • Author(s)
      島田慎吾、深井原,藤堂省, 他
    • Organizer
      第38回日本臓器保存生物医学会
    • Place of Presentation
      仙台;江陽グランドホテル
    • Year and Date
      2011-11-23
  • [Presentation] 臓器の保存から修復への試み~ミトコンドリア機能と細胞内 Ca2+ の重要性2011

    • Author(s)
      深井原,藤堂省, 他
    • Organizer
      第38回日本臓器保存生物医学会
    • Place of Presentation
      仙台;江陽グ ランドホテル
    • Year and Date
      2011-11-23
  • [Presentation] 指定期間に北大病院で施行された成人生体肝移植 61例の検討2010

    • Author(s)
      鈴木友己、嶋村剛、藤堂省, 他
    • Organizer
      第72回日本臨床外科学学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      20101121-23
  • [Presentation] 新規保存液(FJ solution)によるラット肝冷保存再灌流障害の軽減~単離肝灌流を用いた有効成分の検討2010

    • Author(s)
      福森大介、深井原、藤堂省, 他
    • Organizer
      日本移植学会
    • Place of Presentation
      京都; みやこめっせ
    • Year and Date
      20101020-22
  • [Presentation] 新規臓 器保存液(Dsol)のラット心冷保存・移植モデルにおけるグラフト保護効果2010

    • Author(s)
      若山顕治、深井原、藤堂省, 他
    • Organizer
      日本移植学会
    • Place of Presentation
      京都; みやこめっせ
    • Year and Date
      20101020-22
  • [Presentation] 新規臓器保存液の開発;重水とバッファーの細胞保護効果の普遍性と作用メカニズムの検討(in vitro study)2010

    • Author(s)
      深井原、藤堂省,他
    • Organizer
      日本移植学会
    • Place of Presentation
      京都; みやこめっせ]
    • Year and Date
      20101020-22
  • [Presentation] Heavy water containing organ preservation solution, Dsol, ameliorates graft survival and function of the rat hearts afterextended cold preservation2010

    • Author(s)
      Wakayama K, Fukai M, Todo S. et al
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver, Canada; VancouverConvention Centre
    • Year and Date
      20100815-19
  • [Presentation] Important characteristics of heavy water (D2O) containing cold preservation solution2010

    • Author(s)
      Fukai M, Furukawa H, Todo S. et al
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver, Canada; VancouverConvention Centre
    • Year and Date
      20100815-19
  • [Presentation] Extended preservation of rat liver with newly developed organ preservation solution in Hokkaido University2010

    • Author(s)
      Fukumori D, Fukai M, Todo S. et al
    • Organizer
      XXIII International Congress of The Transplantation Society
    • Place of Presentation
      Vancouver, Canada; Vancouver Convention Centre
    • Year and Date
      20100815-19
  • [Presentation] 生体肝移植におけるグラフト選択と肝循環制御法の検討2010

    • Author(s)
      谷口雅彦、藤堂省, 他
    • Organizer
      日本肝移植研究会
    • Place of Presentation
      ANAクラウンプラザホテル広島
    • Year and Date
      20100701-02
  • [Presentation] 新規重水含有臓器保存液による肝長期冷保存・再灌流障害の軽減~重水の肝保護作用を増強する最適条件の探索2010

    • Author(s)
      深井原、藤堂省, 他
    • Organizer
      日本肝移植研究会
    • Place of Presentation
      ANA クラウンプラザホテル広島
    • Year and Date
      20100701-02
  • [Presentation] Functional Classification of Hepatic Veins and Interrelationships among Hepatic Vessels for Living Donor Liver Transprantation2010

    • Author(s)
      Uchida K, Todo S. et al
    • Organizer
      The American Transplant Congress
    • Place of Presentation
      San Diego, USA; San Diego Convention Center
    • Year and Date
      20100501-05
  • [Presentation] Heavy Water(D2O) Universally Ameliorates Cold Preservation Injury: Precise Analyses of Cytoprotective Mechanisms In Vitro2010

    • Author(s)
      Fukai M, Furukawa H, Todo S. et al
    • Organizer
      The American Transplant Congress
    • Place of Presentation
      San Diego, USA; San Diego Convention Center
    • Year and Date
      20100501-05
  • [Presentation] Heavy Water Contaning Solution Ameliorates Cold Preservation Injury of the Rat Heart2010

    • Author(s)
      Wakayama K, Fukai M, Todo S. et al
    • Organizer
      The American Transplant Congress
    • Place of Presentation
      San Diego, USA; San Diego Convention Center
    • Year and Date
      20100501-05
  • [Presentation] ANovel Solution for Rat Liver Preservation Composed of Heavy Water and Swan Buffer; a Pilot Study2010

    • Author(s)
      Fukumori D, Fukai M, Todo S. et al
    • Organizer
      The American Transplant Congress
    • Place of Presentation
      San Diego, USA; San DiegoConvention Center
    • Year and Date
      20100501-05
  • [Book] 移植のための臓器摘出と保存: 浅野武秀監修、福島教偉・剣持敬・絵野沢伸編

    • Author(s)
      深井原、尾崎倫孝 (分担執筆)
    • Publisher
      丸善出版

URL: 

Published: 2014-08-29   Modified: 2015-08-18  

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