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Elucidation of blood cell's response to constant and fluctuating shear stresses

Research Project

Project/Area Number 20K12609
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionShibaura Institute of Technology

Principal Investigator

Watanabe Nobuo  芝浦工業大学, システム理工学部, 教授 (00568644)

Co-Investigator(Kenkyū-buntansha) 福井 浩二  芝浦工業大学, システム理工学部, 教授 (80399807)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords赤血球変形能 / せん断脆弱性 / 血小板活性 / 血液損傷 / せん断応力 / 流れの可視化 / 一様せん断流れ / 変動せん断流れ / 赤血球 / 流動変形 / 高せん断応力 / 画像解析 / 血小板凝集 / 機械式血液循環装置 / 流れの可視化実験 / 血小板凝集能 / せん断負荷 / 心血管デバイス / 血小板 / 血漿タンパク
Outline of Research at the Start

血液ポンプが発生する高せん断応力負荷に対する血液細胞の応答性については、いまだ明らかでない。そこで、申請者はせん断流れの中で血液細胞を可視化する実験装置を構築した。これまでに、赤血球がせん断刺激に応じNO産生する事、加えて過度にせん断刺激を受ければ損傷し異常形状が出現する事を明らかにした。加えて、最近の予備実験から、赤血球損傷時に膜酸化が生じる可能性、および血小板凝集能がせん断条件に応じてピークを示す可能性を示唆するデータを得た。そこで、本研究は更にこれらの研究成果を発展させ、一様せん断条件および心血管デバイス内部を想定した変動せん断条件においての血液細胞のせん断応答性を解明する

Outline of Final Research Achievements

In order to understand blood damage induced by high shear stress, applicants applied his original shear device into international collaborative projects. Morphological abnormalities increased under the condition with high shear stress of 60Pa over 100 seconds exposure time. And image analysis method to detect damaged erythrocyte was successfully proposed (Sci Rep). Blood shear experiments showed correlation among multiple damage parameters, such as von Willebrand factor, platelet activation, and hemolysis (J.Biomech.), and also slight correlation between hemolysis and platelet aggregation(J.Biorheol). Addionally, sinusoidal shear stress generator was successfully developed, and it revealed cyclic deformation change under sinusoidal shear stress (AIP Advances).

Academic Significance and Societal Importance of the Research Achievements

本研究は一様・変動せん断応力下における赤血球単体の変形能およびせん断脆弱性について例示する事ができた。さらに、多数の健常者赤血球の流動変形応答性を検証する事、またそれと対比する事で赤血球変形能低下を伴う病的疾患の診断方法開発へ応用できる可能性が期待される。また、細胞加齢にともなう細胞変形応答性の詳細把握は、赤血球の生理学を前進させる知見につながる可能性がある。さらに、せん断応力の長時間の負荷に対する脆弱性評価も今後可能になり、血液ポンプなどの機械式血液循環装置の血液適合性や、患者血液毎にその赤血球の変形能やせん断脆弱性を考慮したデバイス選定や治療方針をたてる事が可能になる事が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (26 results)

All 2022 2021 2020 Other

All Int'l Joint Research (6 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] Charite病院研究所(ドイツ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Griffith大学/Prince Charles病院研究所(オーストリア)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Griffith University/Prince Charles Hospital(オーストラリア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Charite, University Hospital, Berlin(ドイツ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Griffith University, Gold Coast/University of Queensland, Brisbane/The Prince Charles Hospital, Brisbane(オーストラリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Charite, University Hospital, Berlin(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Direct observation of deformation of individual red blood cells in oscillatory fluid flow produced using a generator of precise sinusoidal shear flow2022

    • Author(s)
      Masnok Kriengsak、Inoue Masataka、Watanabe Nobuo
    • Journal Title

      AIP Advances

      Volume: 12 Issue: 9 Pages: 095020-095020

    • DOI

      10.1063/5.0113873

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro comparative study of activated clotting time in fresh human whole blood with various levels of coagulability using two devices2022

    • Author(s)
      Watanabe Nobuo、Inoue Masataka、Honda Masaki、Masnok Kriengsak、Negishi Teruhiko
    • Journal Title

      Journal of Biorheology

      Volume: 36 Issue: 2 Pages: 39-44

    • DOI

      10.17106/jbr.36.39

    • ISSN
      1867-0466, 1867-0474
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrete responses of erythrocytes, platelets, and von Willebrand factor to shear2022

    • Author(s)
      Chan Chris H.H.、Simmonds Michael J.、Fraser Katharine H.、Igarashi Kosuke、Ki Katrina K.、Murashige Tomotaka、Joseph Mary T.、Fraser John F.、Tansley Geoff D.、Watanabe Nobuo
    • Journal Title

      Journal of Biomechanics

      Volume: 130 Pages: 110898-110898

    • DOI

      10.1016/j.jbiomech.2021.110898

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In vitro comparative study of activated clotting time in fresh human whole blood with various levels of coagulability using two devices2022

    • Author(s)
      N. Watanabe, M. Inoue, M. Honda, K. Masnok, T. Negishi,
    • Journal Title

      Journal of Biorheology

      Volume: 2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Erythrocyte morphological symmetry analysis to detect sublethal trauma in shear flow2021

    • Author(s)
      McNamee Antony P.、Simmonds Michael J.、Inoue Masataka、Horobin Jarod T.、Hakozaki Masaya、Fraser John F.、Watanabe Nobuo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 23566-23566

    • DOI

      10.1038/s41598-021-02936-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Preliminary study of the effect of hemolysis on platelet aggregation through microscopic observation under physiological shear flow2021

    • Author(s)
      Watanabe Nobuo、Kawada Naoki
    • Journal Title

      Journal of Biorheology

      Volume: 35 Issue: 2 Pages: 62-67

    • DOI

      10.17106/jbr.35.62

    • NAID

      130008133903

    • ISSN
      1867-0466, 1867-0474
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shear‐dependent platelet aggregation size2020

    • Author(s)
      Chan Chris Hoi Houng、Inoue Masataka、Ki Katrina K.、Murashige Tomotaka、Fraser John F.、Simmonds Michael J.、Tansley Geoff D.、Watanabe Nobuo
    • Journal Title

      Artificial Organs

      Volume: 44 Issue: 12 Pages: 1286-1295

    • DOI

      10.1111/aor.13783

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Observation of red blood cell's rheological behavior under fluctuating shear conditions using a specially built sinusoidal shear chamber2022

    • Author(s)
      Kriengsak Masnok, Nobuo Watanabe
    • Organizer
      48th Annual European Society for Artificial Organs (ESAO) Congress Austria
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 機械式補助循環を模擬した変動せん断流れ環境下の赤血球観察実験システムの試作2022

    • Author(s)
      松澤ふく大, 大和田将広,井上雅喬,渡邉宣夫
    • Organizer
      第60 回日本人工臓器学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 赤血球の加齢と膜酸化現象の関連性検証2022

    • Author(s)
      久保田玲、福井浩二、渡邉宣夫
    • Organizer
      第75回日本酸化ストレス学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 一様単純せん断流れ発生装置を用いた血液細胞の観察結果から予想される機械式補助循環装置利用環境において生じうる血液損傷現象に対する考察2022

    • Author(s)
      井上雅喬,渡邉宣夫
    • Organizer
      第50回 人工心臓と補助循環懇話会学術集会
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
  • [Presentation] 共焦点蛍光顕微鏡を用いた血小板活性状態の観察‐GPIIb/IIaに着目した血小板活性評価指標の検討‐2022

    • Author(s)
      三浦千代子, 渡邉宣夫
    • Organizer
      第31回ライフサポート学会フロンティア講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 共焦点蛍光顕微鏡を用いた血小板活性状態の観察‐GPIIb/IIaに着目した血小板活性評価指標の検討‐2022

    • Author(s)
      三浦千代子, 渡邉宣夫
    • Organizer
      第31回ライフサポート学会フロンティア講演会,
    • Related Report
      2021 Research-status Report
  • [Presentation] 赤血球の加齢と膜酸化現象の関連性検証2022

    • Author(s)
      久保田玲,福井浩二,渡邉宣夫
    • Organizer
      第75回日本酸化ストレス学会学術集会、
    • Related Report
      2021 Research-status Report
  • [Presentation] Examination of new method to express in detailed expression of plasma vWF for elucidation of their shear stress induced diminishment2021

    • Author(s)
      Reina Kato, Yugo Kato, Koji Fukui, Nobuo Watanabe
    • Organizer
      47th Annual European Society for Artificial Organs(ESAO) Congress, Brunel University, London, Uxbridge, during 7-11 September, 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Asymmetrical erythrocyte morphology to detect sublethal damage2021

    • Author(s)
      Nobuo Watanabe, Antony P. McNamee, Jarod T. Horibin, John F Fraser, Masataka Inoue, Masaya Hakozaki, Fukuta Matsuzawa, Michael J. Simmonds,
    • Organizer
      2nd Joint Meeting of ESCHM-ISCH-ISB Japan
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] せん断流れ下における血小板凝集の顕微鏡観察2021

    • Author(s)
      川田尚輝, 柴田政廣, 渡邉宣夫
    • Organizer
      第44回日本バイオレオロジー学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 止血タンパク研究のための血漿アルブミン除去法の検討2021

    • Author(s)
      加藤玲奈,加藤優吾,福井浩二,渡邉宣夫
    • Organizer
      第44回日本バイオレオロジー学会年会
    • Related Report
      2021 Research-status Report
  • [Remarks] SIT Lab Vol.26血液循環を工学的に再現。赤血球の健康状態を可視化する

    • URL

      https://www.youtube.com/watch?v=1QT9IE2MowI

    • Related Report
      2021 Research-status Report
  • [Remarks] Engineered blood circulation.

    • URL

      https://www.youtube.com/watch?v=La3jraC2nS4

    • Related Report
      2021 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-03-27  

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