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Prolonged functional lifespan of artificial red cells by using the electron energies produced by erythrocyte glycolysis

Research Project

Project/Area Number 25282136
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionNara Medical University

Principal Investigator

SAKAI HIROMI  奈良県立医科大学, 医学部, 教授 (70318830)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Keywords人工酸素運搬体 / 人工赤血球 / リポソーム / ヘモグロビン / 電子伝達物質 / メトヘモグロビン / 輸血代替 / 酸素輸送 / 電子伝達系 / 解糖系 / 血液代替物 / Phenothiazine / 人工血液 / 再生医学 / 生体機能利用 / 生体材料 / 電子移動 / レドックス / ナノバイオ
Outline of Final Research Achievements

In vivo safety and efficacy of artificial red cells (Hb-vesicles, Hb-V) as a transfusion alternative have been clarified extensively. Gradual autoxidation of ferrous Hb in Hb-V to form ferric metHb is inevitable and results in decreased oxygen carrying capacity. We found that metHb in Hb-V can be reduced to ferrous Hb by using the electron energies produced by erythrocyte glycolysis, via methylene blue as a transmembrane electron mediator. We tested other 14 candidate mediators, and found some other potential molecules that can reduce metHb effectively, as did methylene blue. The requisite chemical properties as a potential electron mediator are clarified. We established an indirect enzymatic metHb reducing system for Hb-V using unlimited endogenous electrons created in RBCs in combination with an effective electron mediator that prolongs the functional lifespan of HbV in blood circulation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (14 results)

All 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Lund University(Sweden)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Potential electron mediators to extract electron energies of RBC glycolysis for prolonged in vivo functional lifetime of hemoglobin-vesicles2015

    • Author(s)
      Karin Kettisen, Leif Bülow, Hiromi Sakai
    • Journal Title

      Bioconjugate Chemistry

      Volume: 26 Issue: 4 Pages: 746-754

    • DOI

      10.1021/acs.bioconjchem.5b00076

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 人工赤血球(ヘモグロビンベシクル)の実現に向けて2015

    • Author(s)
      酒井宏水, 久禮智子
    • Journal Title

      医学のあゆみ

      Volume: 253 Pages: 1180-1181

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 人工赤血球(ヘモグロビンベシクル)の実現に向けて2015

    • Author(s)
      酒井宏水、久禮智子
    • Journal Title

      医学のあゆみ

      Volume: -

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Red Blood Cells Donate Electrons to Methylene-blue Mediated Chemical Reduction of Methemoglobin Compartmentalized in Liposomes in Blood.2014

    • Author(s)
      Hiromi Sakai, Bing Li, Wei Lee Lim, Yumika Iga
    • Journal Title

      Bioconjugate Chemistry

      Volume: 25 Issue: 7 Pages: 1301-1310

    • DOI

      10.1021/bc500153x

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Hb-vesicles (赤血球代替物)の有用性と開発の状況2015

    • Author(s)
      酒井宏水
    • Organizer
      第39回日本血液事業学会総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2015-10-05
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Transmembrane electron mediators to extract electron energies of RBC glycolysis for prolonged in vivo functional lifespan of an artificial oxygen carrier (Hb-vesilces)2015

    • Author(s)
      Hiromi Sakai
    • Organizer
      The 10th World Congress for Microcirculation
    • Place of Presentation
      Kyoto International Conference Center
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prolonged in vivo functional lifespan of an artificial oxygen carrier (hemoglobin vesicles) using a transmembrane electron mediator and electron energies of red blood cells glycolysis2015

    • Author(s)
      Hiromi Sakai
    • Organizer
      ICMAT2015 & IUMRS-ICA2015
    • Place of Presentation
      Suntec, Singapore
    • Year and Date
      2015-06-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Translational research of hemoglobin-vesicles as a transfusion alternative2015

    • Author(s)
      Hiromi Sakai
    • Organizer
      International Society on Blood Substitutes (ISBS)
    • Place of Presentation
      Lund University, Sweden
    • Year and Date
      2015-06-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 赤血球解糖系が産生する電子エネルギーの活用による人工赤血球(ヘモグロビンベシクル)の機能持続効果2015

    • Author(s)
      酒井宏水、Karin Kettisen、伊賀弓佳
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      日本大学船橋キャンパス
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Hemoglobin-vesicles for transfusion alternative and oxygen therapeutics2014

    • Author(s)
      H. Sakai
    • Organizer
      International Society on Oxygen Transport to Tissue (ISOTT) 2014
    • Place of Presentation
      University College London, UK
    • Year and Date
      2014-06-28 – 2014-07-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 体内電子供与系の活用による人工赤血球(ヘモグロビン小胞体)の機能復元

    • Author(s)
      酒井宏水、Li Bing、Lim Wei Lee
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋大学 東山キャンパス
    • Related Report
      2013 Annual Research Report
  • [Remarks] 奈良県立医科大学化学教室

    • URL

      http://www.naramed-u.ac.jp/~chem/

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ヘモグロビンのメト化抑制能を有する人工赤血球2016

    • Inventor(s)
      酒井宏水、山田孫平
    • Industrial Property Rights Holder
      酒井宏水、山田孫平
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-040494
    • Filing Date
      2016-03-02
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2019-07-29  

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