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Establishment of therapeutic lymphangiogenesis for lymphedema

Research Project

Project/Area Number 23390208
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal 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) SHINTANI Satoshi  名古屋大学, 医学系研究科, 講師 (20309777)
SHIBATA Rei  名古屋大学, 医学系研究科, 特任講師 (70343689)
Co-Investigator(Renkei-kenkyūsha) KONDO Kazuhisa  名古屋大学, 医学部附属病院, 病院助教 (90644659)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Keywords再生医学 / リンパ浮腫 / リンパ管再生 / リンパ管内皮細胞 / 細胞移植療法 / 間葉系幹細胞 / 脂肪組織由来幹細胞 / サイトカイン / リンパ管 / アディポネクチン / リンパ管再生療法 / 再生医療 / 細胞治療 / 血管新生 / 成長因子 / 脂肪組織由来再生細胞 / マクロファージ
Research Abstract

Lymphedema is a serious clinical problem that occurs after surgical resection of cancers. We report that implantation of adipose-derived regenerative cells (ADRCs) can induce lymphangiogenesis in a mouse model of lymphedema.
ADRCs were isolated from C57BL/6J mice. To examine the efficacy of ADRC implantation in vivo, we established a new mouse model of tail lymphedema. Lymphedema was improved significantly by local injection of ADRCs. Histological analysis revealed that lymphatic capillary density was greater in the ADRC group than in the PBS-injected control group. Tissue expression of vascular endothelial growth factor C (VEGF-C) was greater in the ADRC group than in the control group. ADRCs released VEGF-C, which stimulated lymphangiogenesis. Implantation of ADRCs also enhanced recruitment of M2 macrophages, which served as lymphatic endothelial progenitors. In conclusion, implantation of ADRCs could be a useful treatment option for lymphedema by mediation of lymphangiogenesis.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (36 results)

All 2014 2013 2012 2011

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (17 results) (of which Invited: 1 results)

  • [Journal Article] Adiponectin-mediated modulation of lymphatic vessel formation and lymphedema2013

    • Author(s)
      Shimizu Y, Shibata R, Ishii M, Ohashi K, Kambara T, Uemura Y, Yuasa D, Kataoka Y, Kihara S, Murohara T, Ouchi N
    • Journal Title

      J. Am. Heart Assoc

      Volume: 2

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic reendothelialization by induced pluripotent stem cells after vascular injury--brief report2013

    • Author(s)
      Yamamoto T, Shibata R, Ishii M, Kanemura N, Kito T, Suzuki H, Miyake H, Maeda K, Tanigawa T, Ouchi N, Murohara T
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol

      Volume: 33 Pages: 2218-2221

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis.2013

    • Author(s)
      Kito T, Shibata R, Ishii M, Suzuki H, Himeno T, Kataoka Y, Yamamura Y, Yamamoto T, Nishio N, Ito S, Numaguchi Y, Tanigawa T, Yamashita JK, Ouchi N, Honda H, Isobe K, Murohara T.
    • Journal Title

      Sci Rep

      Volume: 11:3 Issue: 1 Pages: 1418-1418

    • DOI

      10.1038/srep01418

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adipose-derived factor ctrp9 attenuates vascular smooth muscle cell proliferation and neointimal formation2013

    • Author(s)
      Uemura Y, Shibata R, Ohashi K, Enomoto T, Kambara T, Yamamoto T, Ogura Y, Yuasa D, Joki Y, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N
    • Journal Title

      FASEB J

      Volume: 27 Pages: 25-33

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hydrogen sulfide attenuates cardiac dysfunction after heart failure via induction of angiogenesis.2013

    • Author(s)
      Polhemus DJ, Kondo K, Bhushan S, Bir SC, Kevil CG, Murohara T, Lefer DJ, Calvert JW.
    • Journal Title

      Circulation Heart Fail.

      Volume: 6 Pages: 1077-1086

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectin-mediated modulation of lymphatic vessel formation and lymphedema2013

    • Author(s)
      Shimizu Y, Shibata R, Ishii M, Ohashi K, Kambara T, Uemura Y, Yuasa D, Kataoka Y, Kihara S, Murohara T, Ouchi N
    • Journal Title

      J Am Heart Assoc

      Volume: 2 Issue: 5

    • DOI

      10.1161/jaha.113.000438

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Reendothelialization by Induced Pluripotent Stem Cells After Vascular Injury2013

    • Author(s)
      Yamamoto T, Shibata R, Ishii M, Kanemura N, Kito T, Suzuki H, Miyake H, Maeda K, Tanigawa T, Ouchi N, Murohara T
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 33 Issue: 9 Pages: 2218-21

    • DOI

      10.1161/atvbaha.113.301313

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes.2013

    • Author(s)
      Monji A, Mitsui T, Bando YK, Aoyama M, Shigeta T, Murohara T.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol.

      Volume: 305 Issue: 3 Pages: H295-H304

    • DOI

      10.1152/ajpheart.00990.2012

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress augments insulin resistance and prothrombotic state : Role of visceral adipose-derived monocyte chemoattractant protein-12012

    • Author(s)
      Uchida Y, Takeshita K, Yamamoto K, Kikuchi R, Nakayama T, Nomura M, Cheng XW, Egashira K, Matsushita T, Nakamura H, Murohara T
    • Journal Title

      Diabetes

      Volume: 61 Pages: 1552-1561

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic impact of Follistatin-like 1 on myocardial ischemic injury in preclinical animal models2012

    • Author(s)
      Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T
    • Journal Title

      Circulation

      Volume: 126 Pages: 1728-1738

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells2012

    • Author(s)
      Shimizu Y, Shibata R, Shintani S, Ishii M, Murohara T
    • Journal Title

      J. Am. Heart Assoc

      Volume: 1

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fat-derived factor omentin stimulates endothelial cell function and ischemia-induced revascularization via an endothelial nitric oxide synthase-dependent mechanism2012

    • Author(s)
      Maruyama S, Shibata R, Kikuchi R, Izumiya Y, Rokutanda T, Araki S, Kataoka Y, Ohashi K, Daida H, Kihara S, Ogawa H, Murohara T, Ouchi N
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 1 Pages: 408-17

    • DOI

      10.1074/jbc.m111.261818

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells.2012

    • Author(s)
      Yuuki Shimizu
    • Journal Title

      Journal of American Heart Association

      Volume: 1

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic impact of Follistatin-like 1 on myocardial ischemic injury in preclinical animal models.2012

    • Author(s)
      Yasuhiro Ogura
    • Journal Title

      Circulation

      Volume: 126 Pages: 1728-1738

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dipeptidylpeptidase-4 modulates left-ventricular dysfunction in chronic heart failure via angiogenesis-dependent and -independent actions.2012

    • Author(s)
      Toshimasa Shigeta
    • Journal Title

      Circulation

      Volume: 126 Pages: 1838-1851

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The actin-binding protein girdin and its akt-mediated phosphorylation regulate neointima formation after vascular injury2011

    • Author(s)
      Miyake H, Maeda K, Asai N, Shibata R, Ichimiya H, Isotani-Sakakibara M, Yamamura Y, Kato K, Enomoto A, Takahashi M, Murohara T
    • Journal Title

      Circ. Res

      Volume: 108 Pages: 1170-1179

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The actin-binding protein girdin and its akt-mediated phosphorylation regulate neointima formation after vascular injury2011

    • Author(s)
      Miyake H, et al
    • Journal Title

      Circulation Research

      Volume: 108 Pages: 1170-1179

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced angiogenesis by transplantation of mesenchymal stem cell sheet created by a novel magnetic tissue engineering method2011

    • Author(s)
      Ishii M, et al
    • Journal Title

      Arterioscler.Thromb.Vasc.Biol.

      Volume: 31 Pages: 2210-2215

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectin ameliorates doxorubicin-induced cardiotoxicity through an Akt dependent mechanism2011

    • Author(s)
      Maruyama S, et al
    • Journal Title

      J.Biol.Chem.

      Volume: 286 Pages: 32790-32800

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [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
      Miyakomesse, Kyoto, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Notch1 Signaling Regulates Adipogenesis in vivo2013

    • Author(s)
      Motoharu Hayashi, Kyousuke Takeshita, Toyoaki Murohara
    • Organizer
      American Heart Association 2013
    • Place of Presentation
      Dallas Convention Center, Dallas, Texas USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] C1q/Tnf Related Protein9 Prevents Lps Induced Acute Cardiac Injury Through An Ampk Dependent Mechanism2013

    • Author(s)
      Takahiro Kambara, Rei Shibata, Satoko Hayakawa, Takashi Enomoto, Yusuke Uemura, Megumi Miyabe, Yoshiyuki Kataoka, Koji Ohashi, Noriyuki Ouchi, Toyoaki Murohara,
    • Organizer
      American Heart Association 2013
    • Place of Presentation
      Dallas Convention Center, Dallas, Texas USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Comparative Study of Adipose Derived Regenerative Cells versus Bone Marrow-Mononuclear Cells for Therapeutic Angiogenesis2013

    • Author(s)
      Chang-ning Hao, Satoshi Shintani, Yuuki Shimizu, Hong-Xian Wu, Kazuhisa Kondo, Masakazu Ishii, Toyoaki Murohara
    • Organizer
      American Heart Association 2013
    • Place of Presentation
      Dallas Convention Center, Dallas, Texas USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] The Adipokine Omentin Prevents the Pathological Vascular Remodeling2013

    • Author(s)
      Yusuke Uemura, Rei Shibata, Koji Ohashi, Takashi Enomoto, Megumi Miyabe, Yoshiyuki Kataoka, Takahiro Kambara, Kazuhiro Matsuo, Daisuke Yuasa, Yusuke Joki, Satoko Hayakawa, Mizuho Ito, Toyoaki Murohara, Noriyuki Ouchi,
    • Organizer
      American Heart Association 2013
    • Place of Presentation
      Dallas Convention Center, Dallas, Texas USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Adiponectin stimulates lymphangiogenesis and ameliorates secondary lymphedema2012

    • Author(s)
      Shimizu Y, Shibata R, Ohashi K, Ishii M, Shintani S, Murohara T, Ouchi N
    • Organizer
      American Heart Association (AHA) Scientific Sessions 2012
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2012-11-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Adipose-derived regenerative cells implantation alleviates lymphedema via augmentation of VEGF-C mediated M2 macrophage mobilization2012

    • Author(s)
      Shimizu Y, Shintani S, Shibata R, Ishii M, Changning H, Hayashida R, Murohara T
    • Organizer
      American Heart Association (AHA) Scientific Sessions 2012
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2012-11-04
    • Related Report
      2013 Final Research Report
  • [Presentation] A Novel Therapeutic Strategy for Secondary Lymphedema by Adipose-Derived Regenerative Cells2012

    • Author(s)
      Shimizu Y, Shintani S, Shibata R, Ishii M, Changning H, Murohara T
    • Organizer
      Annual Scientific Meeting of the Japanese Circulation Society(第76回日本循環器学会)
    • Place of Presentation
      福岡国際会議場, 福岡市
    • Year and Date
      2012-03-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Adiponectin stimulates lymphangiogenesis and ameliorates secondary lymphedema2012

    • Author(s)
      Yuuki Shimizu
    • Organizer
      American Heart Association 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Adipose-derived Stem Cell Sheets Created by a Novel Magnetite Tissue Engineering Method for Myocardial Infarction2012

    • Author(s)
      Takashi Yamamoto
    • Organizer
      American Heart Association 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Adipose-derived regenerative cells implantation alleviates lymphedema via augmentation of VEGF-C mediated M2 macrophage mobilization2012

    • Author(s)
      Yuuki Shimizu
    • Organizer
      American Heart Association 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development and Remodeling of Newly Formed Blood Vessels in the Specific Hypoxyprobe-positive Area of Infarcted Heart2012

    • Author(s)
      Koichi Kobayashi
    • Organizer
      American Heart Association 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Aav9-wnt11 Gene Therapy Improves Survival of Myocarditis Mice Induced by Coxsackie Virus Through the Improvement of Cardiac Function2012

    • Author(s)
      Yutaka Aoyama
    • Organizer
      American Heart Association 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Implantation of adipose-derived regenerative cells enhances lymphangiogenesis and improves secondary lymphedema2011

    • Author(s)
      Shimizu Y, Shintani S, Shibata R, Izumi Y, Ogura Y, Ishii M, Murohara T
    • Organizer
      American Heart Association (AHA) Scientific Sessions 2011
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-11-14
    • Related Report
      2013 Final Research Report
  • [Presentation] M2 macrophages contribute to postnatal lymphangiogenesis as lymphatic endothelial cell progenitors2011

    • Author(s)
      Shimizu Y, Shintani S, Shibata R, Izumi Y, Ogura Y, Ishii M, Murohara T
    • Organizer
      American Heart Association (AHA) Scientific Sessions 2011
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-11-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells2011

    • Author(s)
      Yuuki Shimizu, et al
    • Organizer
      ESC 2011
    • Place of Presentation
      パリ(招待講演)
    • Year and Date
      2011-08-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells2011

    • Author(s)
      Shimizu Y, Shintani S, Shibata R, Izumi Y, Ogura Y, Ishii M, Murohara T
    • Organizer
      The European Society of Cardiology (ESC) Congress 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-08-28
    • Related Report
      2013 Final Research Report

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Published: 2011-04-06   Modified: 2023-03-16  

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