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Establishment of therapeutic angiogenesis against ischemic cerebravascular disease

Research Project

Project/Area Number 15590785
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

TAGUCHI Akihiko  National Cardiovascular Center Research Institute, Department of Cerebravascular Disease, Group Leader, 循環動態機能部, 室長 (10359276)

Co-Investigator(Kenkyū-buntansha) NARITOMI Hiroaki  National Cardiovascular Center Research Institute, Department of Cerebravascular Disease, Director, 内科脳血管部門, 部長 (60132932)
MATSUYAMA Tomohiro  Hyogo Medical College, Department of Internal Medicine, Associate Prof, 医学部・総合内科, 講師 (10219529)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsStroke / Angiogenesis / Neurogenesis / Stem Cell / 血管血球系細胞 / 血管血球系幹細胞
Research Abstract

The purpose of this study is to assess the hypothesis that EPCs transplantation after stroke prevents brain damage through neovascularization.
We developed a mouse stroke model which is relevant to human cerebral ischemia. EPC-enriched mononuclear cells are transplanted intravenously to mice 48hours after MCA occlusion. As controls, we transplant EPCs-poor mononuclear cells and phosphate-buffered salines. Three months after cell transplantation, we evaluate the mice behaviors by open field test and the regenerated brain area by Triphenyltetorazolium chloride staining. To detect the neovascularization by EPCs transplantation, immunohistological examinations were performed with donor specific anti-CD31 and anti-vWF antibody.
Our results showed that higher capillary densities around ischemic area were observed in the EPCs transplanted mice. Immunohistological examination revealed that transplanted EPCs differentiated into endothelial cells and incorporated into cerebral neovascularization. Regenerated brain area after cerebral ischemia was increased with EPCs transplantation. The mice with EPCs transplantation showed better score in behavior test.
Next, we focused on patients with multiple cerebral infarctions. We have quantified the number of EPCs in peripheral blood by fluorescence activated cell sorter using cell surface marker. It was shown that the turnover rate of endothelial cell is 3 years and 10% of newly formed endothelial cells are bone marrow EPCs origin. Consistent with these previous findings, we have shown that impaired EPCs in peripheral blood are related to the progress of arteriosclerosis through the decreased number of endothelial progenitor cells.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (7 results)

All 2004

All Journal Article (6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Circulating CD34-positive cells provide an index of cerebrovascular function.2004

    • Author(s)
      Taguchi A, Matsuyama T, et al.
    • Journal Title

      Circulation 109

      Pages: 2972-2975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Administration of CD34^+ cells post-stroke enhances angiogenesis and neuroge nesis in a murine model.2004

    • Author(s)
      Taguchi A, Soma T, et al.
    • Journal Title

      J Clin Invest. 114

      Pages: 330-338

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Cadherin activity is required for activity-induced spine remodeling2004

    • Author(s)
      Okamura K, Taguchi A, et al.
    • Journal Title

      J.Cell Biol. 167

      Pages: 961-972

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Administration of CD34+ cells post-stroke enhances neurogenesis via angiogenesis in a mouse model2004

    • Author(s)
      Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T
    • Journal Title

      J.Clin.Invest. 114

      Pages: 330-338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Circulating CD34-positive cells provide an index of cerebrovascular function2004

    • Author(s)
      Taguchi A, Matsuyama T, Moriwaki H, Hayashi T, Hayashida K, Nagatsuka K, Todo K, Mori K, Stern D, Soma T, Naritomi N
    • Journal Title

      Circulation 109

      Pages: 2972-2975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cadherin activity is required for activity-induced spine remodeling2004

    • Author(s)
      Okamura K, Tanaka H, Yagita Y, Saeki Y, Taguchi A, Hiraoka Y, Zeng L, ColmanDR, Miki N
    • Journal Title

      J.Cell Biol. 167

      Pages: 961-972

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 脳梗塞疾患モデルマウス2004

    • Inventor(s)
      松山知弘, 田口明彦他
    • Industrial Property Rights Holder
      科学技術振興機構
    • Industrial Property Number
      2004-108500
    • Filing Date
      2004-03-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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