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Therapeutic angiogenesis using autologous adipose-derived regenerative cells

Research Project

Project/Area Number 26293184
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionNagoya University

Principal Investigator

MUROHARA TOYOAKI  名古屋大学, 医学(系)研究科(研究院), 教授 (90299503)

Co-Investigator(Kenkyū-buntansha) 新谷 理  名古屋大学, 医学(系)研究科(研究院), 寄附講座准教授 (20309777)
柴田 玲  名古屋大学, 医学(系)研究科(研究院), 寄附講座准教授 (70343689)
近藤 和久  名古屋大学, 医学(系)研究科(研究院), 助教 (90644659)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords再生医療 / 血管再生療法 / 幹細胞 / 四肢虚血 / 脂肪組織由来幹細胞 / 血管内皮細胞 / 皮下脂肪組織 / サイトカイン / 血管再生 / 皮下脂肪 / 間葉系幹細胞 / 虚血 / 細胞治療 / 重症四肢虚血 / 血管新生 / 脂肪組織由来再生細胞 / 心筋再生 / 細胞シート / 組織工学 / 心機能 / 虚血性心疾患 / 末梢動脈閉塞症 / 皮下脂肪由来間葉系前駆細胞 / 細胞シート工学
Outline of Final Research Achievements

Our final goal of this research series is to establish the clinical therapeutic angiogenesis in patients with critical limb ischemia manifestating rest pain and/or ischemic skin ulcer due to atherosclerotic disease, Burger's disease and connective tissue diseases such as scleroderma (PSS). To this end, we have established mouse, rat and rabbit model of hind limb ischemia, and we examined the effects of the implantation of autologous adipose-tissue derived regenerative cells (ADRCs), one of the mesenchymal stem cell class, on limb blood perfusion and angiogenesis in these animal models. We also tested the effects of combination of several drugs and ADRCs, H2S on angiogenesis in hind limb ischemia model. We have already performed clinical cases using ADRC injection to patients with critical limb ischemia, and examined the possible biomarkers that can predict the salutary efficacy of this procedure. For example, we are focusing on the role of VEGF-A165b and circulating CD34+ cells.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(31 results)

All 2017 2016 2015 2014

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 7 results,  Acknowledgement Compliant: 6 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Book (5 results)

  • [Journal Article] Diallyl Trisulfide Augments Ischemia-Induced Angiogenesis via an Endothelial Nitric Oxide Synthase-Dependent Mechanism2017

    • Author(s)
      Hayashida R, Kondo K, Morita S, Unno K, Shintani S, Shimizu Y, Calvert JW, Shibata R, Murohara T.
    • Journal Title

      Circ J

      Volume: in press Issue: 6 Pages: 870-878

    • DOI

      10.1253/circj.cj-16-1097

      10.1253/circj.CJ-16-1097

    • NAID

      130005679693

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A dipeptidyl peptidase-4 inhibitor ameliorates hypertensive cardiac remodeling via angiotensin-II/sodium-proton pump exchanger-1 axis.2016

    • Author(s)
      Kawase H, Bando YK, Nishimura K, Aoyama M, Monji A, Murohara T.
    • Journal Title

      J. Mol. Cell. Cardiol.

      Volume: 98 Pages: 37-47

    • DOI

      10.1016/j.yjmcc.2016.06.066

    • NAID

      120005895207

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the p38MAPK and PI3K-Akt/p-HDAC6 Signaling Pathway.2016

    • Author(s)
      Wu H, Cheng XW, Hu L, Takeshita K, Chen H, Du Q, Li X, Zhu E, Huang Z, Yisireyili M, Zhao G, Piao L, Inoue A, Jiang H, Lei Y, Zhang X, Liu S, Dai Q, Kuzuya M, Shi GP, and Murohara T.
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol.

      Volume: 36(8) Pages: 1549-1557

    • DOI

      10.1161/atvbaha.115.307110

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sodium Sulfide Attenuates Ischemic-Induced Heart Failure by Enhancing Proteasomal Function in an Nrf2-Dependent Manner.2016

    • Author(s)
      Shimizu Y, Nicholson CK, Lambert JP, Barr LA, Kuek N, Herszenhaut D, Tan L, Murohara T, Hansen JM, Husain A, Naqvi N, Calvert JW.
    • Journal Title

      Circ. Heart Fail.

      Volume: 9

    • DOI

      10.1161/circheartfailure.115.002368

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response2016

    • Author(s)
      Morishita Y, Kobayashi K, Klyachko E, Jujo K, Maeda K, Losordo DW, Murohara T.
    • Journal Title

      Sci. Rep.

      Volume: 6 Pages: 21705-21705

    • DOI

      10.1038/srep21705

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dipeptidyl Peptidase 4 Inhibition Alleviates Shortage of Circulating Glucagon-Like Peptide-1 in Heart Failure and Mitigates Myocardial Remodeling and Apoptosis via the Exchange Protein Directly Activated by Cyclic AMP 1/Ras-Related Protein 1 Axis2016

    • Author(s)
      Aoyama M, Kawase H, Bando YK, Monji A, Murohara T
    • Journal Title

      Circulation Heart Failure

      Volume: 9

    • DOI

      10.1161/circheartfailure.115.002081

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt-dependent Girdin phosphorylation regulates repair processes after acute myocardial infarction.2015

    • Author(s)
      Hayano S, Takefuji M, Maeda K, Noda T, Ichimiya H, Kobayashi K, Enomoto A, Asai N, Takahashi M, Murohara T.
    • Journal Title

      J. Mol. Cell. Cardiol.

      Volume: 88 Pages: 55-63

    • DOI

      10.1016/j.yjmcc.2015.09.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Girdin/GIV regulates transendothelial permeability by controlling VE-cadherin trafficking through the small GTPase, R-Ras.2015

    • Author(s)
      Ichimiya H, Maeda K, Enomoto A, Weng L, Takahashi M, Murohara T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 461 Pages: 260-267

    • DOI

      10.1016/j.bbrc.2015.04.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] New endoplasmic reticulum stress regulator, gipie, regulates the survival of vascular smooth muscle cells and the neointima formation after vascular injury.2015

    • Author(s)
      Noda T, Maeda K, Hayano S, Asai N, Enomoto A, Takahashi M, Murohara T
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol.

      Volume: 35 Pages: 1246-1253

    • DOI

      10.1161/atvbaha.114.304923

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Therapeutic Angiogenesis by Autologous Adipose-Derived Regenerative Cells: Comparison With Bone Marrow Mononuclear Cells.2014

    • Author(s)
      31.Hao CN, Shintani S, Shimizu Y, Kondo K, Ishii M, Wu H, Murohara T.
    • Journal Title

      American Journal of Physiology, Heart Circ. Physiol.

      Volume: 307

    • DOI

      10.1152/ajpheart.00310.2014

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Multilayered adipose-derived regenerative cell sheets created by a novel magnetic tissue engineering method for myocardial infarction.2014

    • Author(s)
      Ishii M, Shibata R, Shimizu Y, Yamamoto T, Kondo K, Inoue Y, Ouchi N, Tanigawa T, Kanemura N, Ito A, Honda H, Murohara T.
    • Journal Title

      International Journal of Cardiology

      Volume: 175 Pages: 545-53

    • DOI

      10.1016/j.ijcard.2014.06.034

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neuron-derived neurotrophic factor functions as a novel modulator that enhances endothelial cell function and revascularization processes.2014

    • Author(s)
      Ohashi K, Enomoto T, Joki Y, Shibata R, Ogura Y, Kataoka Y, Shimizu Y, Kambara T, Uemura Y, Yuasa D, Matsuo K, Hayakawa S, Hiramatsu-Ito M, Murohara T, Ouchi N.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Pages: 14132-14144

    • DOI

      10.1074/jbc.m114.555789

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cathepsin K-mediated Notch1 activation contributes to neovascularization in response to hypoxia2014

    • Author(s)
      Jiang H, Cheng XW, Shi GP, Hu L, Inoue A, Yamamura Y, Wu H, Takeshita K, Li X, Huang Z, Song H, Asai M, Hao CN, Unno K, Koike T, Oshida Y, Okumura K, Murohara T, Kuzuya M
    • Journal Title

      Nature Communication

      Volume: 5 Pages: 3838-3838

    • DOI

      10.1038/ncomms4838

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease.2014

    • Author(s)
      Kikuchi R, Nakamura K, MacLauchlan S, Ngo DT, Shimizu I, Fuster JJ, Katanasaka Y, Yoshida S, Qiu Y, Yamaguchi TP, Matsushita T, Murohara T, Gokce N, Bates DO, Hamburg NM, Walsh K
    • Journal Title

      Nat. Med.

      Volume: 20(12) Pages: 1464-1471

    • DOI

      10.1038/nm.3703

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Therapeutic angiogenesis by adipose tissue-derived regenerative cells.2016

    • Author(s)
      Kondo K, Shibata R, Hayashida R, Shintani S, Murohara T.
    • Organizer
      Scientific Session, American Heart Association 2016
    • Place of Presentation
      New Orleans, LA, USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of the aging-accelerating Werner protein on glucose metabolism and myocardial remodeling2016

    • Author(s)
      Kawase H, Bando Y, Murohara T.
    • Organizer
      European Society of Cardiology 2016
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Correlations between geriatric nutritional risk index and peripheral artery disease in elderly coronary artery disease patients2016

    • Author(s)
      Suzuki S, Ishii H, Murohara T.
    • Organizer
      European Society of Cardiology 2016
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] C1q/TNF-related protein 1 reduces vascular smooth muscle cell growth and meointimal thickening after vascular injury.2016

    • Author(s)
      Ogawa H, Shibata R, Murohara T, Ouchi N.
    • Organizer
      European Society of Cardiology 2016
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Incretin ameliorates diabetic microangiopathy in heart via suppression of nonanoic acid, a naturally-occurring saturated fatty acid, via activation of AMPK pathway2016

    • Author(s)
      Nishimura K, Bando Y, Murohara T.
    • Organizer
      European Society of Cardiology 2016
    • Place of Presentation
      Roma, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The therapeutic potential of adipose-derived regenerative cell sheets created by a novel magnetite tissue engineering method2016

    • Author(s)
      Rei Shibata
    • Organizer
      第80回日本循環器学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市 )
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Therapeutic angiogenesis by iPS cells2015

    • Author(s)
      Rei Shibata, Toyoaki Murohara
    • Organizer
      第79回日本循環器学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2015-04-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Therapeutic angiogenesis by adipose-derived regenerative cells2014

    • Author(s)
      Rei Shibata, Kazuhisa Kondo, Satoshi Shintani, Toyoaki Murohara
    • Organizer
      第31回国際心臓研究学会(ISHR)日本部会
    • Place of Presentation
      愛知県名古屋市 愛知県産業労働 センター
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Translational Research in Cardiovascular Medicine: Vascular regeneration therapy2014

    • Author(s)
      Toyoaki Murohara
    • Organizer
      第31回国際心臓研究学会(ISHR)日本部会
    • Place of Presentation
      愛知県名古屋市 愛知県産業労働 センター
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Therapeutic Angiogenesis by Cell Transplantation2014

    • Author(s)
      Satoshi Shintani
    • Organizer
      第31回国際心臓研究学会(ISHR)日本部会
    • Place of Presentation
      愛知県名古屋市 愛知県産業労働 センター
    • Year and Date
      2014-11-28 – 2014-11-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] The Comparison of Adipose Derived Regenerative Cells and Bone Marrow Mononuclear Cells as Transplanted Cells for Therapeutic Angiogenesis.2014

    • Author(s)
      Shintani S, Hao C, Shimizu Y, Kondo K, Murohara T.
    • Organizer
      BCVS, American Heart Association
    • Place of Presentation
      Las Vegas, Nevada, USA
    • Year and Date
      2014-07-14 – 2014-07-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cell-based therapeutic angiogenesis for critical limb ischemia2014

    • Author(s)
      Toyoaki Murohara
    • Organizer
      The 18th International Vascular Biology Meeting 2014 (IVBM 2014)
    • Place of Presentation
      京都府京都市 京都市勧業館
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
  • [Book] Therapeutic Angiogenesis2017

    • Author(s)
      Toyoaki Murohara, Kazuhisa Kondo
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Annual Review 2015 循環器2015

    • Author(s)
      坂東泰子、室原豊明
    • Total Pages
      318
    • Publisher
      中外医学社
    • Related Report
      2014 Annual Research Report
  • [Book] EBM 循環器疾患の治療2015

    • Author(s)
      坂東泰子、室原豊明
    • Total Pages
      472
    • Publisher
      中外医学社
    • Related Report
      2014 Annual Research Report
  • [Book] 循環器疾患最新の治療2014-20152014

    • Author(s)
      吉川大治、室原豊明
    • Total Pages
      528
    • Publisher
      南江堂
    • Related Report
      2014 Annual Research Report
  • [Book] 専門医のための循環器病学2014

    • Author(s)
      室原豊明
    • Total Pages
      582
    • Publisher
      医学書院
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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