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Role of Regeneration-Associated Cells in Myocardial Ischemia

Research Project

Project/Area Number 19K08525
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionTokai University

Principal Investigator

Asahara Takayuki  東海大学, 医学部, 客員教授 (20246200)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords再生環境 / 血管再生作用 / 抗炎症作用 / 抗免疫作用 / 心筋梗塞 / 臓器再生 / 再生アソシエイト細胞 / 血管内皮前駆細胞 / 抗炎症マクロファージ / 糖尿病 / 老化 / 再生微小環境 / 再生関連細胞 / 炎症関連細胞 / 制御性T細胞
Outline of Research at the Start

再生治療の開発が進み、ヒトへの臨床応用も始まっている。しかし、疾患による臓器再生環境が改善されていないと、再生治療効果が充分でないことが指摘されている。再生環境の血管再生細胞、マクロファージ・リンパ球の抗炎症・免疫寛容細胞などは、糖尿病・肥満・老化などの慢性炎症病態で機能が低下し再生環境不全を引き起こし動脈硬化症・虚血性疾患の進行に繋がっている。本研究では、健康マウスおよび糖尿病・肥満・老化などのモデルマウスにおける、虚血疾患モデルでの再生環境細胞を病期ごとに分離し、そのフェノタイプ・機能を比較解析する。再生環境不全の病態メカニズムをより効果的な再生医学の発展に繋げる。

Outline of Final Research Achievements

Phenotypes of blood cells in the regenerative microenvironment play an important role in organ and vascular regeneration mechanisms. In chronic inflammatory diseases such as diabetes, obesity, and aging, phenotypic abnormalities in the regenerative microenvironment are thought to cause regenerative environment failure, leading to the progression of atherosclerosis and ischemic diseases. In this study, we isolated regenerative environmental cells in healthy mice and in tissue ischemia models of diabetes, obesity, and aging, and compared their phenotypes and functions. We were able to clarify the dynamics of regenerative environmental cells after myocardial infarction. However, we still need to clarify the mechanism and therapeutic application of these cells.

Academic Significance and Societal Importance of the Research Achievements

糖尿病あるいは高齢による虚血組織における慢性炎症と再生不全は、再生環境細胞の機能不全が大きな原因になっていると考えられ、細胞のフェノタイプ解析によって、それを証明することが出来た。このことは、再生環境細胞の機能不全の原因を探ることで疾患あるいは高齢による治癒不全を治療出来る可能性を示している。その治療薬の開発で、疾患あるいは高齢における健康寿命を大幅に延伸できると期待され、国民の健康生活の質を高め医療費の削減に大いに貢献するものと考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (12 results)

All 2021 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Extracellular Vesicles Derived From Regeneration Associated Cells Preserve Heart Function After Ischemia-Induced Injury2021

    • Author(s)
      Salybekov Amankeldi A.、Salybekova Ainur、Sheng Yin、Shinozaki Yoshiko、Yokoyama Keiko、Kobayashi Shuzo、Asahara Takayuki
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 8 Pages: 1-13

    • DOI

      10.3389/fcvm.2021.754254

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ex vivo conditioning of peripheral blood mononuclear cells of diabetic patients promotes vasculogenic wound healing2021

    • Author(s)
      Tanaka Rica、Ito‐Hirano Rie、Fujimura Satoshi、Arita Kayo、Hagiwara Hiroko、Mita Tomoya、Itoh Masayoshi、Kawaji Hideya、Ogawa Takasuke、Watada Hirotaka、Masuda Haruchika、Asahara Takayuki、Mizuno Hiroshi
    • Journal Title

      STEM CELLS Translational Medicine

      Volume: - Issue: 6 Pages: 895-909

    • DOI

      10.1002/sctm.20-0309

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 32020

    • Author(s)
      Wolfien Markus、Klatt Denise、Salybekov Amankeldi A.、Kawamoto Atsuhiko、Klopsch Christian、Kowallick Johannes T.、Krebs Stefan、Nesteruk Julia、Reichenspurner Hermann、Ritter Christian、Stamm Christof、Tani-Yokoyama Ayumi、Blum Helmut、Wolkenhauer Olaf、Schambach Axel、Asahara Takayuki、Steinhoff Gustav
    • Journal Title

      EBioMedicine

      Volume: 57 Pages: 102862-102862

    • DOI

      10.1016/j.ebiom.2020.102862

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overview of Basic Mechanisms of Notch Signaling in Development and Disease2020

    • Author(s)
      McIntyre Brendan、Asahara Takayuki、Alev Cantas
    • Journal Title

      Adv Exp Med Biol

      Volume: - Pages: 9-27

    • DOI

      10.1007/978-3-030-36422-9_2

    • ISBN
      9783030364212, 9783030364229
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-inflammatory and vasculogenic conditioning of peripheral blood mononuclear cells reinforces their therapeutic potential for radiation-injured salivary glands.2019

    • Author(s)
      I T, Sumita Y, Yoshida T, Honma R, Iwatake M, Raudales JLM, Shizuno T, Kuroshima S, Masuda H, Seki M, Tran SD, Asahara T, Asahina I.
    • Journal Title

      Stem Cell Res Ther.

      Volume: 10 Issue: 1 Pages: 304-304

    • DOI

      10.1186/s13287-019-1414-7

    • NAID

      120006988389

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insufficient production of IL-10 from M2 macrophages impairs in vitro endothelial progenitor cell differentiation in patients with Moyamoya disease.2019

    • Author(s)
      Nagata E, Masuda H, Nakayama T, Netsu S, Yuzawa H, Fujii N, Kohara S, Sorimachi T, Osada T, Imazeki R, Matsumae M, Asahara T, Takizawa S.
    • Journal Title

      Sci Rep

      Volume: 9(1) Issue: 1 Pages: 16752-16752

    • DOI

      10.1038/s41598-019-53114-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vasculogenically conditioned peripheral blood mononuclear cells inhibit mouse immune response to induced pluripotent stem cell-derived allogeneic cardiac grafts2019

    • Author(s)
      Kashiyama Noriyuki、Miyagawa Shigeru、Fukushima Satsuki、Kawamura Takuji、Kawamura Ai、Yoshida Shohei、Nakamura Yuki、Harada Akima、Masuda Haruchika、Toda Koichi、Asahara Takayuki、Sawa Yoshiki
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 5 Pages: e0217076-e0217076

    • DOI

      10.1371/journal.pone.0217076

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Batroxobin accelerated tissue repair via neutrophil extracellular trap regulation and defibrinogenation in a murine ischemic hindlimb model2019

    • Author(s)
      Masuda Haruchika、Sato Atsuko、Shizuno Tomoko、Yokoyama Keiko、Suzuki Yusuke、Tokunaga Masayoshi、Asahara Takayuki
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 8 Pages: e0220898-e0220898

    • DOI

      10.1371/journal.pone.0220898

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systemic administration of quality- and quantity-controlled PBMNCs reduces bisphosphonate-related osteonecrosis of the jaw-like lesions in mice2019

    • Author(s)
      Kuroshima S, Nakajima K, Sasaki M, Takashi I, Y Sumita, Asahara T, Asahina I, Sawase T
    • Journal Title

      Stem Cell Res Ther.

      Volume: 10 Issue: 1 Pages: 209-209

    • DOI

      10.1186/s13287-019-1308-8

    • NAID

      120006988442

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Current update of endothelial progenitor cell biology and medicine2021

    • Author(s)
      T. Asahara
    • Organizer
      International Society of Applied Cardiovascular Biology
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 血管内皮前駆細胞を用いた血管再生療法の開発2021

    • Author(s)
      浅原孝之
    • Organizer
      日本再生医療学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 再生アソシエイト細胞の再生・抗炎症作用2021

    • Author(s)
      浅原孝之
    • Organizer
      日本炎症・再生医学会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2023-01-30  

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