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Development of new strategy for the treatment of cardiovascular disease using adipose tissue.

Research Project

Project/Area Number 20K08401
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Shibata Rei  名古屋大学, 医学系研究科, 特任教授 (70343689)

Co-Investigator(Kenkyū-buntansha) 室原 豊明  名古屋大学, 医学系研究科, 教授 (90299503)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血管新生 / 重症虚血肢 / 脂肪組織由来間葉系前駆細胞 / 幹細胞 / 創傷治癒
Outline of Research at the Start

「脂肪組織由来間葉系前駆細胞を用いた重症虚血肢に対する血管新生療法」が効果を示す、その機序解明と優位性の評価を行う逆トランスレーショナルリサーチの遂行。具体的には、以下の4点に関して検討を行う。
1) ADRCsを用いた血管新生療法の治療効果を予測するバイオマーカーの探索
2) 創傷治癒におけるADRCsの役割検討
3) ADRCsを用いた血管新生療法の治療効果の機序解明
4) 生活習慣病がADRCsの血管新生療法へ及ぼす影響の検討

Outline of Final Research Achievements

The ageing of the population has led to a marked increase in the number of patients with cardiovascular disease. Angiogenic therapy is becoming established as a new treatment strategy for such cases. In our study, transplantation of Adipose-derived Regenerative Cells in patients with severe ischemic limbs resulted in reduced pain and ulcer size, and amputation of the affected limb was avoided. Possible mechanisms include modulation of VEGF secretion, suppression of inflammation and promotion of wound healing. The results also showed that VEGF-A isoforms and zinc levels in the blood may be promising predictors of the therapeutic effect.

Academic Significance and Societal Importance of the Research Achievements

重症虚血肢患者では、切断を余儀なくされる症例は少なくない。切断を選択する前の新たな治療選択肢として、今回我々が行った「脂肪組織由来間葉系前駆細胞を用いた重症虚血肢に対する血管新生療法」が一定の効果を示した。また、その機序に関しても、その一部が明らかとなった。これらの成果は、「心血管系に対する安全で効果的な再生医療」の確立につながると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020

All Journal Article (15 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Omentin Modulates Chronic Cardiac Remodeling After Myocardial Infarction2023

    • Author(s)
      Ito M, Shibata R, Ohashi K, Otaka N, Yamaguchi S, Ogawa H, Enomoto T, Masutomi T, Murohara T, Ouchi N.
    • Journal Title

      Circulation Reports

      Volume: 5 Issue: 2 Pages: 46-54

    • DOI

      10.1253/circrep.CR-22-0079

    • ISSN
      2434-0790
    • Year and Date
      2023-02-10
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic angiogenesis for patients with no-option critical limb ischemia by adipose-derived regenerative cells: TACT-ADRC multicenter trial2022

    • Author(s)
      Shimizu Yuuki、Kondo Kazuhisa、Takashima Shinichiro、Inoue Oto、Usui Soichiro、Takamura MasayukiMitsukawa Nobuyuki、Akita Shinsuke、Ebisawa Soichiro、the TACT-ADRC multicenter trial Group
    • Journal Title

      Angiogenesis

      Volume: 25 Issue: 4 Pages: 535-546

    • DOI

      10.1007/s10456-022-09844-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct reprogramming of adult adipose-derived regenerative cells toward cardiomyocytes using six transcriptional factors2022

    • Author(s)
      Narita Shingo、Unno Kazumasa、Kato Katsuhiro、Okuno Yusuke、Sato Yoshitaka、Tsumura Yusuke、Fujikawa Yusuke、Shimizu Yuuki、Hayashida Ryo、Kondo Kazuhisa、Shibata Rei、Murohara Toyoaki
    • Journal Title

      iScience

      Volume: 25 Issue: 7 Pages: 104651-104651

    • DOI

      10.1016/j.isci.2022.104651

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrogen Sulfide Attenuates Lymphedema Via the Induction of Lymphangiogenesis Through a PI3K/Akt‐Dependent Mechanism2022

    • Author(s)
      Suzuki Junya、Shimizu Yuuki、Hayashi Takumi、Che Yiyang、Pu Zhongyue、Tsuzuki Kazuhito、Narita Shingo、Shibata Rei、Ishii Isao、Calvert John W.、Murohara Toyoaki
    • Journal Title

      Journal of the American Heart Association

      Volume: 11 Issue: 21

    • DOI

      10.1161/jaha.122.026889

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adipose-derived regenerative cells as a promising therapy for cardiovascular diseases: an overview2022

    • Author(s)
      Yamaguchi Shukuro、Shimizu Yuki、Murohara Toyoaki、Shibata Rei.
    • Journal Title

      Nagoya Journal of Medical Science

      Volume: 84 Issue: 2 Pages: 208-215

    • DOI

      10.18999/nagjms.84.2.208

    • ISSN
      0027-7622
    • URL

      https://nagoya.repo.nii.ac.jp/records/2002873

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zinc deficiency impairs ischemia-induced angiogenesis2022

    • Author(s)
      Tsuruoka Takuya、Kodama Akio、Yamaguchi Shukuro、Masutomi Tomohiro、Koyama Akio、Murohara Toyoaki、Komori Kimihiro、Shibata Rei
    • Journal Title

      JVS-Vascular Science

      Volume: 3 Pages: 30-40

    • DOI

      10.1016/j.jvssci.2021.09.023

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Future of Therapeutic Angiogenesis Using Adipose-Derived Stem Cells in the Cardiovascular Field2021

    • Author(s)
      Shibata Rei、Murohara Toyoaki
    • Journal Title

      Circulation Journal

      Volume: 85 Issue: 5 Pages: 667-668

    • DOI

      10.1253/circj.CJ-21-0172

    • NAID

      130008028998

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2021-04-23
    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intramyocardial Transplantation of Human iPS Cell?Derived Cardiac Spheroids Improves Cardiac Function in Heart?Failure Animals2021

    • Author(s)
      Kawaguchi Shinji、Soma Yusuke、Nakajima Kazuaki、Kanazawa Hideaki、Tohyama Shugo、Tabei Ryota、Hirano Akinori、Handa Noriko、Yamada Yoshitake、Okuda Shige,...........Shibata Rei、Murohara Toyoaki、Tabata Yasuhiko、Kobayashi Eiji、Shimizu Hideyuki、Fukuda Keiichi、Fujita Jun
    • Journal Title

      JACC: Basic to Translational Science

      Volume: 6 Issue: 3 Pages: 239-254

    • DOI

      10.1016/j.jacbts.2020.11.017

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Important Role of Concomitant Lymphangiogenesis for Reparative Angiogenesis in Hindlimb Ischemia.2021

    • Author(s)
      Pu Z, Shimizu Y, Tsuzuki K, Suzuki J, Hayashida R, Kondo K, Fujikawa Y, Unno K, Ohashi K, Takefuji M, Bando YK, Ouchi N, Calvert JW, Shibata R, Murohara T.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: - Issue: 6 Pages: 2006-2018

    • DOI

      10.1161/atvbaha.121.316191

    • NAID

      120007178394

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Omentin attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-knockout mice2021

    • Author(s)
      Fang Lixin、Ohashi Koji、Otaka Naoya、Ogawa Hayato、Hiramatsu-Ito Mizuho、Kawanishi Hiroshi、Bando Yasuko K、Shibata Rei、Shimizu Yuuki、Kato Katsuhiro、Takikawa Tomonobu、Ozaki Yuta、Takefuji Mikito、Murohara Toyoaki、Ouchi Noriyuki
    • Journal Title

      Cardiovascular Research

      Volume: ー Issue: 6 Pages: 1597-1610

    • DOI

      10.1093/cvr/cvab179

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adverse Effect of Circadian Rhythm Disorder on Reparative Angiogenesis in Hind Limb Ischemia2021

    • Author(s)
      Tsuzuki Kazuhito、Shimizu Yuuki、Suzuki Junya、Pu Zhongyue、Yamaguchi Shukuro、Fujikawa Yusuke、Kato Katsuhiro、Ohashi Koji、Takefuji Mikito、Bando Yasuko K.、Ouchi Noriyuki、Calvert John W.、Shibata Rei、Murohara Toyoaki
    • Journal Title

      Journal of the American Heart Association

      Volume: 10 Issue: 16

    • DOI

      10.1161/jaha.121.020896

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] No influence on tumor growth by intramuscular injection of adipose-derived regenerative cells: safety evaluation of therapeutic angiogenesis with cell therapy2021

    • Author(s)
      Suzuki Junya、Shimizu Yuuki、Tsuzuki Kazuhito、Pu Zhongyue、Narita Shingo、Yamaguchi Shukuro、Katagiri Takeshi、Iwata Etsuo、Masutomi Tomohiro、Fujikawa Yusuke、Shibata Rei、Murohara Toyoaki
    • Journal Title

      American Journal of Physiology-Heart and Circulatory Physiology

      Volume: 320 Issue: 1 Pages: 447-457

    • DOI

      10.1152/ajpheart.00564.2020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Angiogenesis Using Bone Marrow Mononuclear Cell Transplantation ― A New Standard Treatment for Thromboangiitis Obliterans? ―2020

    • Author(s)
      Shibata Rei、Yamaguchi Shukuro、Murohara Toyoaki
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 4 Pages: 549-550

    • DOI

      10.1253/circj.CJ-20-0137

    • NAID

      130007815657

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-03-25
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic angiogenesis using autologous adipose-derived regenerative cells in patients with critical limb ischaemia in Japan: a clinical pilot study2020

    • Author(s)
      Katagiri Takeshi、Kondo Kazuhisa、Shibata Rei、Hayashida Ryo、Shintani Satoshi、Yamaguchi Shukuro、Shimizu Yuuki、Unno Kazumasa、Kikuchi Ryosuke、Kodama Akio、Takanari Keisuke、Kamei Yuzuru、Komori Kimihiro、Murohara Toyoaki
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 16045-16045

    • DOI

      10.1038/s41598-020-73096-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] C1q/TNF-Related Protein 9 Promotes Revascularization in Response to Ischemia via an eNOS-Dependent Manner2020

    • Author(s)
      Yamaguchi Shukuro、Shibata Rei、Ohashi Koji、Enomoto Takashi、Ogawa Hayato、Otaka Naoya、Hiramatsu-Ito Mizuho、Masutomi Tomohiro、Kawanishi Hiroshi、Murohara Toyoaki、Ouchi Noriyuki
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 1313-1313

    • DOI

      10.3389/fphar.2020.01313

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Development of new strategy for the treatment of cardiovascular disease using adipose tissue.2022

    • Author(s)
      Shibata Rei
    • Organizer
      CVMW2022 心血管代謝週間
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 血管新生における亜鉛の役割2021

    • Author(s)
      柴田玲
    • Organizer
      第21回日本抗加齢医学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] C1q/TNF-Related Protein 9 Stimulates Revascularization in Response to Ischemia Through an eNOS-Dependent Pathway2020

    • Author(s)
      Shukuro Yamaguchi, Rei Shibata, Koji Ohashi, Toyoaki Murohara, and Noriyuki Ouchi
    • Organizer
      The 4th JCS Council Forum on Basic CardioVascular Research 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 皮膚保護剤2021

    • Inventor(s)
      山本徳則、柴田玲、室原豊明、西村賢治、加藤真貴子
    • Industrial Property Rights Holder
      山本徳則、柴田玲、室原豊明、西村賢治、加藤真貴子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 皮膚保護剤2021

    • Inventor(s)
      山本徳則、柴田玲、室原豊明、加藤真貴子、山城知佳
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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