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The molecular mechanism of blood cell-cell interaction forming niche inducing CD34+ cell expansion and differentiation to endothelial progenitor cells in vascular regeneration

Research Project

Project/Area Number 25461091
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionTokai University

Principal Investigator

MASUDA Haruchika  東海大学, 医学部, 准教授 (50278496)

Co-Investigator(Renkei-kenkyūsha) ASAHARA Takayuki  東海大学, 医学部, 教授 (20246200)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords血管内皮前駆細胞 / CD34 / Notchシステム / 血管再生 / 単球 / 血液細胞間ニッチ / Notch リガンド / Notchリガンド
Outline of Final Research Achievements

We investigated blood cell-cell interactions to promote the expansion and differentiation of endothelial progenitor cells (EPCs) derived from CD34+ cells using the novel culture system developed by our laboratory. Peripheral blood mononuclear cells are divided into CD34+ stem cells, and CD34- cells of T lymphocytes (CD3+ cells), and monocytes (CD14+ cells). We found the promoting effect of CD34- cell populations on vascular regeneration capability of CD34+ cells via expansion and differentiation to endothelial progenitor cells (EPCs). Further, CD14+ cells turned out to be a key cell population responsible for the effect through a direct cell-cell interaction of Notch ligand/receptor system, Delta like -1 expressed on CD14+ cells to Notch receptor-1, or 2 on CD34+ cells, but not CD3+ cells.
The results indicate that CD34+ cells together with CD14+ cells form the functional ‘niche’ playing a critical role in vascular regeneration, providing a novel information in vascular biology.

Report

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

    (18 results)

All 2016 2014 2013 2012

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (6 results) (of which Invited: 1 results) Book (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Recent Progress in Endothelial Progenitor Cell Culture Systems: Potential for Stroke Therapy2016

    • Author(s)
      S. Takizawa, E. Nagata, T. Nakayama, H. Masuda, T. Asahara. Recent Progress in Endothelial Progenitor Cell Culture Systems: Potential for Stroke Therapy. Neurol Med Chir (Tokyo). 2016;
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 56 Issue: 6 Pages: 302-309

    • DOI

      10.2176/nmc.ra.2016-0027

    • NAID

      130005157735

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasculogenic conditioning of peripheral blood mononuclear cells promotes endothelial progenitor cell expansion and phenotype transition of anti-inflammatory macrophage and T lymphocyte to cells with regenerative potential.2014

    • Author(s)
      H. Masuda, R. Tanaka, S. Fujimura, M. Ishikawa, H. Akimaru, T. Shizuno, A. Sato, Y. Okada, Y. Iida, J. Itoh, Y. Itoh, H. Kamiguchi, A. Kawamoto, T. Asahara.
    • Journal Title

      J Am Heart Assoc.

      Volume: 3 Issue: 3

    • DOI

      10.1161/jaha.113.000743

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dextran induces differentiation of circulating endothelial progenitor cells.2014

    • Author(s)
      S. Obi, H. Masuda, H. Akimaru, T. Shizuno, K. Yamamoto, J. Ando, and T. Asahara
    • Journal Title

      Physiol. Rep.

      Volume: 2 Issue: 3 Pages: e00261-e00261

    • DOI

      10.1002/phy2.261

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 抗炎症・血管・組織再生性細胞群としての培養末梢血単核球の再生医療応用2014

    • Author(s)
      増田治史
    • Journal Title

      日本血栓止血学会雑誌

      Volume: 25 Pages: 593-602

    • NAID

      130004700437

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clonogenic assay of endothelial progenitor cells2013

    • Author(s)
      Masuda H, Asahara T
    • Journal Title

      Trends Cardiovasc Med

      Volume: 23 Issue: 4 Pages: 99-103

    • DOI

      10.1016/j.tcm.2012.09.007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of mouse colony-forming endothelial progenitor cells for postnatal neovascularization: A novel insight highlighted by new mouse colony-forming assay2013

    • Author(s)
      Tsukada S, Masuda H, Asahara T
    • Journal Title

      Stem Cell Res Ther

      Volume: 4 Issue: 1 Pages: 20-20

    • DOI

      10.1186/scrt168

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quality-control culture system restores diabetic endothelial progenitor cell vasculogenesis and accelerates wound closure.2013

    • Author(s)
      Tanaka, R. Vaynrub, M. Masuda, H. Ito, R. Kobori, M. Miyasaka, M. Mizuno, H. Warren, S. M. Asahara, T.
    • Journal Title

      Diabetes

      Volume: 62 Issue: 9 Pages: 3207-3217

    • DOI

      10.2337/db12-1621

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ex-vivo expanded human blood-derived CD133(+) cells promote repair of injured spinal cord2013

    • Author(s)
      Naosuke Kamei, Mitsuo Ochi
    • Journal Title

      Journal of the Neurological Sciences

      Volume: in press Issue: 1-2 Pages: 41-50

    • DOI

      10.1016/j.jns.2013.02.013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Miyasaka M. Autologous g-csf mobilized peripheral blood cd34(+) cell therapy for diabetic patients with chronicnon-healing ulcer2012

    • Author(s)
      Tanaka R, Masuda H, Asahara T
    • Journal Title

      Cell Transplant

      Volume: 23 Issue: 2 Pages: 167-179

    • DOI

      10.3727/096368912x658007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 血管内皮前駆細胞を主体とした末梢血濃縮細胞群(QQ-EPCs)による萎縮唾液腺再生療法の開発2016

    • Author(s)
      井 隆司、住田吉慶、増田治史、浅原孝之、朝比奈泉
    • Organizer
      第15回 日本再生医療学会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Establishment of Serum-Free Culture System of Peripheral Blood Mononuclear Cells to Potentiate Vascular Regeneration2014

    • Author(s)
      Masuda H, Tanaka R, Fujimura S, Ishikawa M, Akimaru H, Shizuno T, Kawamoto A, Asahara T.
    • Organizer
      第11回国際幹細胞研究学会 (International Society of Stem Cell Research Conference)
    • Place of Presentation
      ボストンコンベンションセンター
    • Related Report
      2013 Research-status Report
  • [Presentation] Vasculogenic Culture of Blood Mononuclear Cell Enhances Regenerative and Anti-inflammatory Potential2014

    • Author(s)
      Masuda H, Tanaka R, Fujimura S, Ishikawa M, Akimaru H, Shizuno T, Kawamoto A, Asahara T.
    • Organizer
      第13回日本再生医療学会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
  • [Presentation] Vasculogenic Conditioning of Peripheral Blood Mononuclear Cells Coordinates Regenerative Potential via Expanding Endothelial Progenitor Cells, Anti-inflammatory Macrophages and T lymphocytes2014

    • Author(s)
      Masuda H, Tanaka R, Fujimura S, Ishikawa M, Akimaru H, Shizuno T, Kawamoto A, Asahara T.
    • Organizer
      第78回日本循環器学会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report
  • [Presentation] Vasculogenic Conditioning of Peripheral Blood Mononuclear Cells Coordinates Tissue Regeneration Associating Cells2014

    • Author(s)
      Masuda H, Tanaka R, Fujimura S, Ishikawa M, Akimaru H, Shizuno T, Kawamoto A, Asahara T.
    • Organizer
      国際血管生物学会(International Vascular Biology Meeting)
    • Place of Presentation
      京都みやこメッセ
    • Related Report
      2013 Research-status Report
  • [Presentation] 血管内皮前駆細胞と血管再生、組織再生2013

    • Author(s)
      増田治史
    • Organizer
      第14回phrmaco-Hematologyシンポジウム
    • Place of Presentation
      東京(渋谷) 長井記念ホール
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] Endothelial Progenitor Cell, Vascular Medicine2013

    • Author(s)
      増田治史
    • Total Pages
      8
    • Publisher
      先端医学社
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 血管内皮前駆細胞を含む細胞群の生体外増幅方法2013

    • Inventor(s)
      浅原孝之、増田治史、田中里佳
    • Industrial Property Rights Holder
      浅原孝之、増田治史、田中里佳
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-09-28
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] 血管内皮前駆細胞を含む細胞群の生体外増幅方法2013

    • Inventor(s)
      浅原孝之、増田治史、田中里佳
    • Industrial Property Rights Holder
      浅原孝之、増田治史、田中里佳
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-09-30
    • Related Report
      2013 Research-status Report
    • Overseas

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Published: 2014-07-25   Modified: 2019-07-29  

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