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Application of artificial oxygen-carrying hemoglobin vesicles for marginal liver grafts in machine perfusion preservation

Research Project

Project/Area Number 17K10503
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionAsahikawa Medical College

Principal Investigator

Matsuno Naoto  旭川医科大学, 医学部, 特任教授 (00231598)

Co-Investigator(Kenkyū-buntansha) 酒井 宏水  奈良県立医科大学, 医学部, 教授 (70318830)
小原 弘道  首都大学東京, システムデザイン研究科, 准教授 (80305424)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肝臓保存 / 機械灌流保存 / 人工赤血球 / 移植臓器保存液 / 心停止ドナー肝 / 臓器灌流保存 / 心肺停止ドナー / 虚血再灌流障害 / 1肝臓灌流保存 / 2心停止ドナー / 3人工赤血球含有灌流液 / 4虚血再灌流障害 / 移植・再生医療
Outline of Final Research Achievements

Pig livers were excised after 60 minutes of warm ischemic time and were preserved under one of three preservation conditions for 4 hours. The preservation conditions were as follows: cold storage (CS group; N = 5), Hypothermic machine preservation (HMP) (HMP group; N = 5), subnormothermic MP (21゜C) ; N = 5) SNMP with HbVs (SNMP+HbV group; N = 5). Autologous blood perfusion was performed for 2 hours in an isolated liver reperfusion model). The oxygen consumption of the SNMP and SNMP +HbV group was higher than the HMP groups (p < 0.05). During the reperfusion, AST level in the SNMP+HbV group was lower than that in the CS, HMP and SNMP groups. The changes in pH was significantly lower in SNMP+HbV group. The ultrastructural findings indicated that the mitochondria of the SNMP+HbV group was well maintained. The SNMP +HbVs preservation solution protected against metabolic acidosis and preserved the liver function after reperfusion injury in the DCD liver.

Academic Significance and Societal Importance of the Research Achievements

研究成果は、ブタを用いた前臨床的研究であること、灌流保存技液による臓器機能回復をめざした点で我が国初の画期的研究成果だと考えている。臓器移植手術では、移植直前に臓器内血球成分を洗い流すため、人工赤血球が体内に入ることはなく、臨床応用のハードルは高くないと考えている。今回、虚血再灌流障害を抑制することに成功した。心停止肝臓のみならず、小児医療などで期待の高い分割肝あるいは脂肪肝など適用に課題のある臓器移植を可能とする可能性がある。赤血球循環技術はdrug delivery systemや臓器培養、再生医療との共創により次世代型治療との複合による新しい時代の研究を切り開くプラットフォームになる

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (26 results)

All 2020 2019 2018 2017

All Journal Article (15 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death2020

    • Author(s)
      Hiromichi Obara, Noriyuki Morito, Naoto Matsuno, Ryo Yoshikawa, Tetsuya Nakajo, Mikako Gochi, Masahide Otani, Tatsuya Shonaka, Hiroyuki Furukawa
    • Journal Title

      Journal of Artificial Organs

      Volume: 23 Issue: 1 Pages: 62-69

    • DOI

      10.1007/s10047-019-01123-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of Machine Perfusion on Sinusoid Microcirculation of Liver Graft Donated After Cardiac Death.2020

    • Author(s)
      Kanazawa H, Obara H, Yoshikawa R, Meng L, Hirano T, Okada Y, Nishikawa Y, Matsuno N.
    • Journal Title

      J Surg Res

      Volume: 245 Pages: 410-419

    • DOI

      10.1016/j.jss.2019.07.058

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Applicability of Hypothermic Oxygenate Machine Perfusion Preservation for Split-Liver Transplantation in a Porcine Model: An Experimental Study2020

    • Author(s)
      Ishii Daisuke、Matsuno Naoto、Gochi Mikako、Otani Masahide、Shonaka Tatsuya、Takahashi Hiroyuki、Nishikawa Yuji、Yoshikawa Ryo、Obara Hiromichi、Miyamoto Kazutoshi、Furukawa Hiroyuki
    • Journal Title

      Annals of Transplantation

      Volume: 25 Pages: 1-8

    • DOI

      10.12659/aot.919920

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 免疫抑制剤と臓器保存 Current topics of immunosuppression and preservation for organ transplantation2020

    • Author(s)
      松野直徒、庄中達也、高橋裕之、萩原正弘、今井浩二、横尾英樹、合地美香子、大谷将秀、古川博之、石井大介、小原弘道
    • Journal Title

      日中医学

      Volume: Vol.35 No.1 Pages: 2-7

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model.2019

    • Author(s)
      T. Shonaka, N. Matsuno, H. Obara, R. Yoshikawa, Y. Nishikawa, Y. Ishihara, H. Bochimoto, M. Gochi, M. Otahi, H. Kanazawa, H. Azuma, H. Sakai, H. Fukuhara
    • Journal Title

      PLOS ONE

      Volume: 14(12) Issue: 12 Pages: 1-17

    • DOI

      10.1371/journal.pone.0226183

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 機械灌流による代謝に着目した移植のための臓器機能評価技術、 Organ viability assessment technology using machine perfusion for transplantation.2019

    • Author(s)
      小原弘道、吉川 遼、松野直徒、中條哲也、絵野沢 伸、平野俊彦
    • Journal Title

      Organ Biology 2019

      Volume: Vol26 No2 Pages: 123-128

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Oxygen consumption during hypothermic and subnormothermic machine perfusions of porcine liver grafts after cardiac death2018

    • Author(s)
      Morito Noriyuki、Obara Hiromichi、Matsuno Naoto、Enosawa Shin、Furukawa Hiroyuki
    • Journal Title

      Journal of Artificial Organs

      Volume: 21 Issue: 4 Pages: 450-457

    • DOI

      10.1007/s10047-018-1063-0

    • Related Report
      2018 Research-status Report
  • [Journal Article] Current development of organ assessment method using machine perfusion for organ transplantation2018

    • Author(s)
      小原 弘道
    • Journal Title

      Organ Biology

      Volume: 25 Issue: 2 Pages: 192-196

    • DOI

      10.11378/organbio.25.192

    • NAID

      130007418412

    • ISSN
      1340-5152, 2188-0204
    • Related Report
      2018 Research-status Report
  • [Journal Article] Evaluation Using an Isolated Reperfusion Model for Porcine Liver Donated After Cardiac Death Preserved with Oxygenated Hypothermic Machine Perfusion2018

    • Author(s)
      Yoshikawa Ryo、Matsuno Naoto、Morito Noriyuki、Gouchi Mikako、Otani Masahide、Takahashi Hiroyuki、Shonaka Tatsuya、Nishikawa Yuji、Enosawa Shin、Hirano Toshihiko、Furukawa Hiroyuki、Obara Hiromichi
    • Journal Title

      Annals of Transplantation

      Volume: 23 Pages: 822-827

    • DOI

      10.12659/aot.910008

    • Related Report
      2018 Research-status Report
  • [Journal Article] 心停止ドナーへの肝移植に対する人工赤血球(Hemoglobin vesicles, HbV)を用いた灌流保存方法の有効性2018

    • Author(s)
      庄中 達也、松野 直徒、小原 弘道、吉川 遼、西川 祐司、合地 美香子、大谷 将秀、高橋 裕之、東 寛、酒井 宏水、古川 博之
    • Journal Title

      北海道外科雑誌

      Volume: 63 Pages: 46-48

    • NAID

      40021786031

    • Related Report
      2018 Research-status Report
  • [Journal Article] The application of perfusate with human-derived oxygen carrier solution under subnormothermic machine perfusion for donation after cardiac death (DCD) liver grafts in pigs2017

    • Author(s)
      Tatsuya Shonaka, Naoto Matsuno, Hiromichi Obara, Ryo Yoshikawa, Yuji Nishikawa,Mikako Goucha, Masahide Otana, Hiroyuki Takahashi, Hiroshi Azuma, Hiromi Sakai, Hiroyuki Furukawa
    • Journal Title

      Transpl Proc

      Volume: Transpl Proc Issue: 9 Pages: 2821-2825

    • DOI

      10.1016/j.transproceed.2018.02.184

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation2017

    • Author(s)
      Bochimoto H, Matsuno N, Ishihara Y, Shonaka T, Koga D, Hira Y, Nishikawa Y, Furukawa H, Watanabe T
    • Journal Title

      PLos One

      Volume: 12 Issue: 10 Pages: e0186352-e0186352

    • DOI

      10.1371/journal.pone.0186352

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 北海道から発信する移植医療技術;臓器灌流保存、機能再生プロジェクトについて2017

    • Author(s)
      松野直徒、庄中達也、合地美香子、大谷将秀、大原みずほ、高橋裕之、小原弘道、西川祐司、古川博之
    • Journal Title

      北海道外科雑誌

      Volume: VOL.62

    • Related Report
      2017 Research-status Report
  • [Journal Article] 臓器機械灌流による臓器機能評価技術の新展開2017

    • Author(s)
      小原弘道、松野直徒、吉川遼、森戸規之、森井勇太、絵野沢伸、平野俊彦
    • Journal Title

      Organ Biology

      Volume: Organ Biology

    • NAID

      130007418412

    • Related Report
      2017 Research-status Report
  • [Journal Article] Ex vivo reperfusion model to evaluate the utility of machine preservation for porcine liver donated after cardiac death2017

    • Author(s)
      Ryo Yoshikawa; Hiromichi Obara; Naoto Matsuno; Noriyuki Morito; Mikako Gouchi; Masahide Otani; Tatsuya Shonaka; Hiroyuki Takahashi; Shin Enosawa; Toshihiko Hirano; Hiroyuki Furukawa
    • Journal Title

      Transpl Proc

      Volume: Transpl Proc Issue: 9 Pages: 2826-2829

    • DOI

      10.1016/j.transproceed.2018.04.020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Present status of transplant organ preservation by dynamic machine perfusion system: How important is the development of a novel organ preservation solution?2019

    • Author(s)
      Naoto Matsuno
    • Organizer
      第26回日本血液代替物学会年次大会 同時開催 第17回血液代替物国際会議―The 17th International Symposium on Blood Substitutes and Oxygen Therapeutics(ⅩⅤⅡ-ISBS-2019)(奈良県)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The efficacy of hemoglobin vesicles(HbV)containing solution in machine perfusion in donation after cardiac death(DCD) in pig liver model2019

    • Author(s)
      Tatsuya Shonaka、Naoto Matsuno、Hiromichi Obara、Ryo Yoshikawa、Yuji Nishikawa、Yo Ishihara、Hiroki Bochimoto、Mikako Gochi、Masahide Otani、Hiroyuki Kanazawa、Hiroshi Azuma、Hiromi Sakai、Hiroyuki Furukawa
    • Organizer
      第26回日本血液代替物学会年次大会 同時開催 第17回血液代替物国際会議―The 17th International Symposium on Blood Substitutes and Oxygen Therapeutics(ⅩⅤⅡ-ISBS-2019)(奈良県)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 命をつなぐ移植臓器灌流保存方法における人口赤血球(HbV)含有灌流保存液の研究2018

    • Author(s)
      松野 直徒、庄中 達也、金澤 寛之、合地 美香子、大谷 将秀、高橋 裕之、西川 祐司、小原 弘道、暮地本 宙己、酒井 宏水、古川 博之、東 寛
    • Organizer
      第25回日本血液代替物学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 臓器機能温存に貢献する新しい医工学技術」S2-4 肝臓代謝因子に着目した室温機械灌流における移植前機能評価の基礎的検討2018

    • Author(s)
      吉川 遼、小原 弘道、松野 直徒、金澤 寛之、中篠 哲也、長谷川 海地、渡辺 大智、森戸 規之、絵野沢 伸、平野 俊彦、古川 博之
    • Organizer
      第45回日本臓器保存生物医学会学術集会(名古屋)
    • Related Report
      2018 Research-status Report
  • [Presentation] (小崎正巳教授メモリアルシンポジウム)「次世代の臓器保存」 S4-5 国内臨床応用に向けた臓器機械灌流保存の有効性に関する検討2018

    • Author(s)
      金澤 寛之、小原 弘道、松野 直徒、吉川 遼、合地 美香子、石井 大介、長谷川 海地、渡辺 大智、絵野沢 伸、平野 俊彦、古川 博之
    • Organizer
      第45回日本臓器保存生物医学会学術集会(名古屋)
    • Related Report
      2018 Research-status Report
  • [Presentation] The examination of perfusate with arfificial oxygen carrier under subnormothermic machine perfusion for DCD liver grafts in pigs.2017

    • Author(s)
      Tatsuya Shounaka
    • Organizer
      15thCongress of the Asian Society of Transplantation Poster presentation
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 長期間保存された人工赤血球による肝灌流保存液の基礎的検討2017

    • Author(s)
      庄中 達也
    • Organizer
      第53回 日本移植学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 人工赤血球含有灌流液による肝機械灌流保存の基礎的検討2017

    • Author(s)
      庄中 達也
    • Organizer
      第53回 日本移植学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝移植モデルを用いた人工赤血球含有灌流液での肝機械灌流保存の基礎的検討2017

    • Author(s)
      庄中 達也
    • Organizer
      第44回日本臓器保存生物医学会学術集会
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] CONNECTOR AND FLUID SUPPLY SYSTEM2019

    • Inventor(s)
      M Matsumura, N Matsuno et al.
    • Industrial Property Rights Holder
      M Matsumura, N Matsuno et al.
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 機械保存装置2017

    • Inventor(s)
      小原弘道、松野直徒
    • Industrial Property Rights Holder
      小原弘道、松野直徒
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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