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Exsercise intervation improves bone marrow niche and endothelial progenitor cell defects in stroke

Research Project

Project/Area Number 17K01881
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied health science
Research InstitutionKindai University

Principal Investigator

NIWA Atsuko  近畿大学, 医学部, 講師 (60122082)

Co-Investigator(Kenkyū-buntansha) 西中 崇  近畿大学, 医学部, 助教 (50786184)
高橋 英夫  近畿大学, 医学部, 教授 (60335627)
小堀 宅郎  近畿大学, 医学部, 助教 (60734697)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsCD34+ 血球・血管系前駆細胞 / 骨髄微小環境(ニッチ) / 血管内皮細胞 / 運動 / 低酸素 / 炎症 / 脳卒中 / 血管新生 / 血管性ニッチ / CD34+骨髄細胞 / 運動介入 / 恒常性 / 再生修復 / FGF2 / regeneration / 臓器連関 / 生体恒常性 / ニッチ因子 / 血管系幹細胞/前駆細胞 / 間葉系細胞 / 骨髄血管 / 骨髄 / 微小環境(ニッチ) / 血管系幹細胞・前駆細胞
Outline of Final Research Achievements

Bone marrow (BM) endothelial phenotypes were shaped by stroke. As BM endothelial cells are an important component of BM niche, alterations of endothelial cells influence BM stem cell function. Stroke-prone hypertensive rats impaired hypoxia condition and sinusoidal vessels after stroke. BM endothelial and mesencymal stromal cells impaired the production of SDF-1 and FGF-2, leading to decrease CD34+ hematopoietic progenitor cell (HSPC) activity (decreasing retension, proliferation and mobilization). Exercise induced niche remodeling in associattion with the increased production of SDF-1 and FGF and regulates the retension and differentiation of HSPC, followed restration of HSPC pool. Inflammatory myelopoiesis and endothelial dysfunction (including repair impairment) driving cronic inflammation are propelled by alterations of the hematopoietic niche. Cross talk between BM endothelia and stem cells is a potential target for the development of anti-inflammatory cerebrovascular treatment.

Academic Significance and Societal Importance of the Research Achievements

脳卒中に至る過程で骨髄ジヌソイド血管内皮細胞は形態的および機能的に劣化した。骨髄血管内皮細胞は、血球・血管系幹細胞/前駆細胞の重要なニッチ細胞の一つであり、血管病における炎症性白血球の増多と組織血管内皮細胞の修復能低下を介して内皮機能障害に関与する可能性がある。運動介入は、骨髄血管系内皮細胞と間葉系細胞の血管性ニッチを改善し、造血系細胞分化と増殖の制御や血球・血管系幹細胞/前駆細胞の増殖と骨髄内の保持の制御、また末梢への動員を促進した。これは、身体活動による生体の内在的な修復能を介した臓器連関の活性化と骨髄内皮細胞・造血系幹細胞の相互作用の制御が慢性炎症性血管病の治療標的となる可能性を示した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (16 results)

All 2020 2019 2018 Other

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

  • [Journal Article] Effects of Scavenger Receptor-1 Class A Stimulation on Macrophage Morphology and Highly Modified Advanced Glycation End Product-Protein Phagocytosis.2018

    • Author(s)
      Hamasaki S, Kobori T, Yamazaki Y, Kitaura A, Niwa A, Nishinaka T, Nishibori M, Mori S, Nakao S, Takahashi H
    • Journal Title

      Scientific Reports

      Volume: s Issue: 1 Pages: 5901-5901

    • DOI

      10.1038/s41598-018-24325-y

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Interleukin-18 Amplifies Macrophage Polarization and Morphological Alteration, Leading to Excessive Angiogenesis.2018

    • Author(s)
      Kobori T, Hamasaki S, Kitaura A, Yamazaki Y, Nishinaka T, Niwa A, Nakao S, Wake H, Mori S, Yoshino T, Nishibori M, Takahashi H
    • Journal Title

      Frontiers in Immunology

      Volume: 9 Pages: 334-334

    • DOI

      10.3389/fimmu.2018.00334

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Alterations of lymphocyte count and platelet volume precede development of stroke-related symptoms in stroke-prone spontaneously hypertensive rats2020

    • Author(s)
      NishinakaT, Niwa A, Wake H, Mori S, Nishibori M, Takahashi H
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] FGF signaling promotes bone marrow niche remodeling in post-stroke recovery2019

    • Author(s)
      Niwa A, Akahoshi Y, Horiuchi Y, Nishinaka T, Takahashi H
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] マクロファージによる終末糖化産物の取り込みに対する硫酸化多糖類の影響2018

    • Author(s)
      西中 崇、山﨑 由衣、丹羽 淳子、森 秀治、和氣 秀徳、西堀 正洋、髙橋 英夫
    • Organizer
      第134回日本薬理学会近畿部会
    • Related Report
      2018 Research-status Report
  • [Presentation] Advanced glycation end products による血管新生促進機序の解明2018

    • Author(s)
      山﨑 由衣、西中 崇、丹羽 淳子、森 秀治、和氣 秀徳、西堀 正洋、髙橋 英夫
    • Organizer
      第134回日本薬理学会近畿部会
    • Related Report
      2018 Research-status Report
  • [Presentation] Exercise intervention improves bone marrow niche and endothelial progenitor cell defects in stroke2018

    • Author(s)
      Niwa A, Akahoshi Y, Nishinaka T, Takahashi H
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY (国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Visualization of advanced glycatiion end products phagocytosis by macrophages and identification of possible receptor2018

    • Author(s)
      Hamasaki S, Kobori T, Kitaura A, Yamazaki Y, Nishinaka T, Niwa A, Nakao S, Nishibori M, Takahashi H
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY (国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of histidine-rich glycoprotein (HRG) production under the experimental pathological conditions2018

    • Author(s)
      Teshigawara K, Niwa A, Wake H, Liu K, Mori S, Takahashi H, Nishibori M
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY (国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Screening of sulfated polysaccharide and sugar-related compounds as the regulator of advanced glycation end-products by macrophages2018

    • Author(s)
      Nishinaka T, Kobori T, Hamasaki S, Kitaura A, Niwa A, Mori S, Nishibori M, Takahashi H
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY (国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Interleukin-18 amplifies M2 polarization of macrophage which leads excessive angiogenesis2018

    • Author(s)
      Yamazaki Y, Kobori T, Niwa A, Nishinaka T, Mori S, Nishibori M, Takahashi H
    • Organizer
      18th WORLD CONGRESS OF BASIC AND CLINICAL PHARMACOLOGY (国際学会)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] マクロファージと血管内皮細胞の細胞間相互作用による血管新生促進機構の解析2018

    • Author(s)
      小堀 宅郎、濱﨑 真一、北浦 淳寛、山崎 由衣、西中 崇、丹羽 淳子、西堀 正洋、髙橋 英夫
    • Organizer
      第138回日本薬理学会関東部会
    • Related Report
      2017 Research-status Report
  • [Presentation] Exercise intervation improves bone marrow niche and endothelial progenitor cell defects in stroke.2018

    • Author(s)
      Niwa A, Akahoshi Y, Nishinaka T, Kobori T, Takahashi H
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] https://www.med.kindai.ac.jp/pharma/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 近畿大学医学部薬理学教室

    • URL

      https://www.med.kindai.ac.jp/pharma/

    • Related Report
      2018 Research-status Report
  • [Remarks] 近畿大学医学部薬理学教室

    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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