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2009 Fiscal Year Final Research Report

Artificial Red Cells : Physiological Importance of the Ligand Reaction Dynamism and the New Application for Ligand Therapy

Research Project

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Project/Area Number 19300164
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionWaseda University

Principal Investigator

SAKAI Hiromi  Waseda University, 理工学術院, 准教授 (70318830)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Koichi  慶應義塾大学, 医学部 (80051704)
Project Period (FY) 2007 – 2009
Keywords人工臓器工学 / 人工赤血球
Research Abstract

Chemically modified hemoglobin (Hb) solutions as artificial O_2 carriers show vasoconstriction and hypertension presumably due to the high affinity for endogenous NO and CO as vasorelaxation factors, and due to the faster O_2-release that induces autoregulatory vasoconstriction. On the other hand, cellular-type Hb-vesicle (HbV) does not induce such side effects. Herein we analyzed the reactions of ligand gaseous molecules by physicochemical techniques, and found out that HbV shows much slower reactions and it is due to the intracellular gas diffusion barrier induced by a concentrated Hb solution, and the retarded lateral diffusion of HbV when it flows in a narrow tube. In addition, we tested HbV as an exogenous CO carrier because endogenous CO is cytoprotective. After inducing hemorrhagic shock, rats were resuscitated with CO-bound HbV. It showed cytoprotective effect at reperfusion, and CO was dissociated rapidly and exhaled through the lung. No symptom related to toxicity of CO was detected. The results imply the possibility of artificial red cells for a new ligand therapy.

  • Research Products

    (23 results)

All 2010 2009 2008 2007 2006 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (5 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Hemoglobin encapsulation in vesicles retards NO-and CO-bindings and O2-release when perfused through narrow gas-permeable tubes.2010

    • Author(s)
      H. Sakai, N. Okuda, A. Sato, S. Takeoka, E. Tsuchida.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol. 298

      Pages: H956-H965

    • Peer Reviewed
  • [Journal Article] Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic murine skin.2009

    • Author(s)
      J.A. Plock, N. Rafatmehr, D. Sinovcic, Y. Harder, H. Sakai, E. Tsuchida, A. Banic, D. Erni.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol. 297

      Pages: H905-910

    • Peer Reviewed
  • [Journal Article] Histopathological changes of rat brain after direct injection of hemoglobin-vesicles (oxygen carriers) and neurological impact in an intracerebral hemorrhage model2009

    • Author(s)
      H. Sakai, M. Okamoto, E. Ikeda, H. Horinouchi, K. Kobayashi, E. Tsuchida.
    • Journal Title

      J. Biomed. Mater. Res. 90A

      Pages: 1107-1119

    • Peer Reviewed
  • [Journal Article] Mechanism of flocculate formation of highly concentrated phospholipid vesicles suspended in a series of water-soluble biopolymers.2009

    • Author(s)
      H. Sakai, A. Sato, S. Takeoka, E. Tsuchida.
    • Journal Title

      Biomacromolecules 10

      Pages: 2344-2350

    • Peer Reviewed
  • [Journal Article] Peculiar flow patterns of RBCs suspended in viscous fluids and perfused through a narrow tube (25μm).2009

    • Author(s)
      H. Sakai, A. Sato, N. Okuda, S. Takeoka, N. Maeda, E. Tsuchida
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol. 297

      Pages: H583-H589

    • Peer Reviewed
  • [Journal Article] Static structure and dynamics of hemoglobin vesicles (HbV) developed as a transfusion alternative2009

    • Author(s)
      T. Sato, H. Sakai, K. Sou, O. Glatter, E. Tsuchida.
    • Journal Title

      J. Phys. Chem. B. 113

      Pages: 8418-8428

    • Peer Reviewed
  • [Journal Article] Hemoglobin-vesicles and red blood cells as carriers of carbon monoxide prior to oxygen for resuscitation after hemorrhagic shock in a rat model2009

    • Author(s)
      H. Sakai, H. Horinouchi, K. Kobayashi, E. Tsuchida.
    • Journal Title

      Shock 31

      Pages: 507-514

    • Peer Reviewed
  • [Journal Article] Fluid resuscitation with artificial oxygen carriers in hemorrhaged rats: Profiles of Hb-vesicles degradation and hematopoiesis for 14 days2009

    • Author(s)
      H. Sakai, Y. Seishi, Y. Obata, S. Takeoka, H. Horinouchi, E. Tsuchida, K. Kobayashi.
    • Journal Title

      Shock 31

      Pages: 192-200

    • Peer Reviewed
  • [Journal Article] The role of luminal factors in the recovery of gastric functions and behavioral changes after chronic Helicobacter pylori infection.2008

    • Author(s)
      E.F. Verdu, P. Bercik, X.X. Huang, J. Lu, N. Al-Mutawaly, H. Sakai, T.A. Tompkins, K. Croitoru, E. Tsuchida, M. Prude, S.M. Collins.
    • Journal Title

      Am. J. Physiol. Gastrointest. Liver Physiol. 295

      Pages: G664-G670

    • Peer Reviewed
  • [Journal Article] NO and CO binding profiles of hemoglobin vesicles as artificial oxygen carriers.2008

    • Author(s)
      H. Sakai, A. Sato, P. Sobolewski, S. Takeoka, J.A. Frangos, K. Kobayashi, M. Intaglietta, E. Tsuchida.
    • Journal Title

      Biochim. Biophys. Acta 1784

      Pages: 1441-1447

    • Peer Reviewed
  • [Journal Article] Encapsulation of concentrated hemoglobin solution in phospholipid vesicles retards the reaction with NO, but not CO, by intracellular diffusion barrier2008

    • Author(s)
      H. Sakai, A. Sato, K. Masuda, S. Takeoka, E. Tsuchida.
    • Journal Title

      J. Biol. Chem. 283

      Pages: 1508-1517

    • Peer Reviewed
  • [Journal Article] Hemoglobin-vesicles as artificial oxygen carriers: Present situation and future vision.2008

    • Author(s)
      H. Sakai, K. Sou, H. Horinouchi, K. Kobayashi, E. Tsuchida.
    • Journal Title

      J. Intern. Med. 263

      Pages: 4-15

    • Peer Reviewed
  • [Journal Article] 各種代用血漿剤に分散させたヘモグロビン小胞体(人工赤血球)とその血液混合系のレオロジー特性2007

    • Author(s)
      佐藤敦、酒井宏水、武岡真司、土田英俊
    • Journal Title

      日本ヘモレオロジー学会誌 10

      Pages: 3-11

    • Peer Reviewed
  • [Journal Article] Rheological properties of hemoglobin vesicles (artificial oxygen carriers) suspended in a series of plasma substitute solutions2007

    • Author(s)
      H. Sakai, A. Sato, S. Takeoka, E. Tsuchida
    • Journal Title

      Langmuir 23

      Pages: 8121-8128

    • Peer Reviewed
  • [Presentation] Physicochemical characteristics of Hb-Vesicles as RBC substitutes2009

    • Author(s)
      H. Sakai, K. Sou, H. Horinouchi, K. Kobayashi, E. Tsuchida.
    • Organizer
      XII International Symposium on Blood Substitutes
    • Place of Presentation
      Parma
    • Year and Date
      20090825-20080828
  • [Presentation] Hemoglobin-vesicles as O2- and CO carriers2008

    • Author(s)
      H. Sakai, H. Horinouchi, K. Kobayashi, E. Tsuchida
    • Organizer
      The 6th Current Issues on Blood Substitute Research
    • Place of Presentation
      Keio University Shinanomachi Campus
    • Year and Date
      20081024-20081025
  • [Presentation] Hb-Vesicle: A Cellular Hb-Based Oxygen Carrier that Fulfills the Physiological Roles of the RBC Structure2008

    • Author(s)
      H. Sakai, K. Sou, H. Horinouchi, K. Kobayashi, E. Tsuchida
    • Organizer
      ISOTT 2008 (Intenational Society on Oxygen Transport to Tissue)
    • Place of Presentation
      Sapporo Prince Hotel
    • Year and Date
      20080803-20080807
  • [Presentation] Hb-vesicles as artificial oxygen carriers: Interactions with ligand molecules in the production process and in blood circulation.2007

    • Author(s)
      H. Sakai, H. Horinouchi, K. Kobayashi, E. Tsuchida.
    • Organizer
      2007 Joint Congress of the 45th Annual Meeting of the Japanese Society for Artificial Organs (JSAO) and The 2nd Meeting of the International Federation for Artificial Organs (IFAO)
    • Place of Presentation
      Osaka
    • Year and Date
      20071028-20071031
  • [Presentation] Hemoglobin vesicles as artificial oxygen carriers: Interactions with ligand molecules in the production process and in blood circulation.2007

    • Author(s)
      H. Sakai, A. Sato, K. Sou, H. Horinouchi, K. Kobayashi, E. Tsuchida.
    • Organizer
      The 11th International Symposium on Blood Substitutes
    • Place of Presentation
      Beijing, China
    • Year and Date
      20071018-20071021
  • [Book] Oxygen Transport to Tissue XXXI(Hemoglobin-vesicle, a cellular artificial oxygen carrier, that fulfils the physiological roles of the red blood cells structure).2010

    • Author(s)
      H. Sakai, K. Sou, H. Horinouchi, K. Kobayashi, E. Tsuchida
    • Total Pages
      433-438
    • Publisher
      Adv. Exp. Med. Biol.
  • [Book] Hemoglobin vesicles as a transfusion alternative2009

    • Author(s)
      H. Sakai, K. Sou, E. Tsuchida
    • Total Pages
      465,363-384
    • Publisher
      Methods Enzymol
  • [Remarks]

    • URL

      www.waseda.jp/prj-artifblood/index-ja.html

  • [Patent(Industrial Property Rights)] 配位子置換型酸素輸液剤2006

    • Inventor(s)
      酒井宏水, ほか
    • Industrial Property Rights Holder
      (財)生産開発科学研究所
    • Patent Publication Number
      公開特許公報特開2007-269665
    • Filing Date
      2006-03-30

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Published: 2011-06-18   Modified: 2016-04-21  

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