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Therapeutic angiogenesis by transplantation of peripheral blood-derived mononuclear cells and platelets

Research Project

Project/Area Number 14570701
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKansai Medical University

Principal Investigator

KAMIHATA Hiroshi  Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60233946)

Co-Investigator(Kenkyū-buntansha) MATSUBARA Hiroaki  Kansai Medical University, Faculty of Medicine, Associate Professor, 医学研究科, 教授 (10239072)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsangiogenesis / stem cells / regenerative medicine / bone marrow / vasculogenesis / regeneration
Research Abstract

Peripheral blood-mononuclear cells(PBMNC), platelets or polymorphonuclear leukocytes(PMN) contain various angiogenic factors. PBMNC-10^7+platelets-10^9, PBMNC-10^7+platelets-10^9+PMN-10^7 were intramuscularly implanted into the ischemic limbs of athymic nude rats. Neocapillary formation was induced in PBMNC+platelet-implanted limbs, while PMN attenuated it. Cellular extract from PBMNC+platelets markedly stimulated tubule formation of HUVEC, which was inhibited by anti-VEGF neutralizing antibody. Neutrophil elastase inhibitor blocked the anti-angiogenic action of PMN. This study demonstrated that implanatation of PBMNC and platelets into ischemic limbs effectively induces collateral vessel formation by supplying angiogenic factors, suggesting that this cell therapy is useful as a novel strategy for therapeutic angiogenesis.
The feasibility of catheter-based implantation of peripheral blood(PB)-MNC into ischemic hibernating myocardium was investigated. Ischemic area, systolic function, regional blood flow and neocapillary formation were significantly improved. Thus, catheter-based implantation of PB-MNC can effectively improve collateral perfusion and regional function in hibernating ischemic myocardium.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Fujiyama S, Amano K, Matsubara H., 他6人: "Bone marrow monocyte lineage-cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells"Circ Res. 93. 980-989 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano K, Matsubara H, 他6名: "Enhancement of Ischemia-Induced Angiogenesis by eNOS overexpression."Hypertension. 41. 156-162 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tateishi-Yuyama E, Matsubara H, 他7名: "Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone marrow cells : a pilot study and a randomised controlled trial"Lancet. 360. 427-435 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iba O, Matsubara H, 他5名: "Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs."Circulation. 106. 2019-2025 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamihata H, Matsubara H, 他6名: "Improvement of Collateral Perfusion and Regional Function by Catheter-Based Implantation of Peripheral Blood Mononuclear Cells into Ischemic Hibernating Myocardium"Arterioscler Thromb Vasc Biol. 22. 1804-1810 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yang Z, Matsubara H, 他7名: "Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction."Circulation. 106. 106-111 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiyama S, Amano K, Matsubara H.: "Bone Marrow Monocyte-Lineage Cells Adhere on Injured Endothelium by MCP-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells"Circ Res. 93. 980-989 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Amano K, Matsubara H.Iba O, Fujiyama S, Mori Y, Kojima H, Iwasaka T: "Enhancement of Ischemia-Induced Angiogenesis by eNOS overexpression."Hypertension. 41. 156-162 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsubara H.: "Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation"Lancet. 361. 49 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Shimada K, Iwasaka T, Imaizumi T: "Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone marrow cells : a pilot study and a randomised controlled trial"Lancet. 360. 427-435 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iba O, Matsubara H, Nozawa Y, Fujiyama S, Amano.K, Kojima H, IwasakaT.: "Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs."Circulation. 106. 2019-2025 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamihata H, Matsubara H, Nishiue N, Fujiyama S, Amano K, Mori Y, Kojima H, Iwasaka T: "Improvement of Collateral Per fusion and Regional Function by Catheter-Based Implantation of Peripheral Blood Mononuclear Cells into Ischemic Hibernating Myocardium"Arterioscler Thromb Vase Biol. 22. 1804-1810 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yang Z, Bove CM, French BA, Epstein FH, Berr SS, DiMaria JM, Gibson JJ, Matsubara H, Carey RM.: "Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction."Circulation. 106. 106-111 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, Iwasaka T.: "Implantation of autologous bone marrow cells into ischemic myocardium enhances collateral perfusion and regional function via side-supply of angioblasts, angiogenic ligands and cytokines"Circulation. 104. 1046-1052 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiyama S, Matsubara H, Mori Y, Iwasaka T.: "Angiotensin AT1 and AT2 Receptors Differentially Regulate Angiopoietin 2 Expression and VEGF Expression and Angiogenesis by Modulating Heparin Binding EGF-Mediated EOF Receptor Transactivation"Circ Res. 88. 22-29 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shibasaki Y, Matsubara H, Nozawa Y, Mori Y, Masaki H, Kosaki A, Tsutsumi Y, Uchiyama Y, Fujiyama S, Nose A, Iba O, Tateishi E, Hasegawa T, Horiuchi M, Nahmias C, Iwasaka T.: "Angiotensin II Type 2 Receptor Inhibits EGF Receptor Transactivation by Increasing Association of SHP-1 Tyrosine Phosphatase"Hypertension. 38. 367-372 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Uchiyama-Tanaka Y, Matsubara H, Nozawa Y, Murasawa S, Mori Y, Kosaki A, Maruyama K, Masaki H, Shibasaki Y, Fujiyama S, Nose A, Iba O, Hasagawa T, Tateishi E, Higashiyama S, Iwasaka T.: "Angiotensin II signaling and HB-EGF shedding via metalloproteinase in glomerular mesangial cells."Kidney Int.. 60. 2153-2163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsubara H, Shibasaki Y, Okigaki M, Mori Y, Masaki H, Kosaki A, Tsutsumi Y, Uchiyama Y, Fujiyama S, Nose A, Iba O, Tateishi E, Hasegawa T, Horiuchi M, Nahmias C, Iwasaka T.: "Effect of angiotensin II type 2 receptor on tyrosine kinase Pyk2 and c-Jun NH2-terminal kinase via SHP-1 tyrosine phosphatase activity : evidence from vascular-targeted transgenic mice of AT2 receptor"Biochem Biophys Res Commun. 282. 1085-1091 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Murasawa S, Matsubara H, Mori Y, Masaki H, Tsutsumi Y, Shibasaki Y, Kitabayashi I, Tanaka Y, Fujiyama S, Kqyama Y, Fujiyama A, Iba S, Iwasaka T.: "Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase."J Biol Chem. 275. 26856-26863 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsutusmi Y, Matsubara H, Masaki H, Mori Y, Maruyama K, Murasawa S, Moriguchi Y, Shibazaki Y, Tanaka Y, Takahashi H, Iwasaka T: "Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation"J Clin Invest. 104. 925-935 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masaki H, Kurihara T, Yamaki A, Inomata N, Nozawa Y, Mori Y, Murasawa S, Kizima K, Maruyama K, Horiuchi M, Dzau VJ, Takahashi H, Iwasaka T, Inada M, Matsubara H.: "Cardiac-Specific Overexpression of Angiotensin AT2 receptor Causes Attenuated Response to ATI receptor-Mediated Pressor and Chronotropic Effects"J Clin Invest. 101. 527-535 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujiyama S, Amano K, Matsubara H. 他6人: "Bone Marrow Moriocyte-Lineage Cells Adhere on Injured Endothelium by MCP-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells"Circ Res. 93. 980-989 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Amano K, Matsubara H, 他6人: "Enhancement of Ischemia-Induced Angiogenesis by eNOS overexpression."Hypertension. 41. 156-162 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tateishi-Yuyama E, Matsubara H, 他7人: "Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone marrow cells : a pilot study and a randomised controlled trial"Lancet. 360. 427-435 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iba O, Matsubara H, 他5人: "Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs."Circulation. 106. 2019-2025 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kamihata H, Matsubara H, 他6人: "Improvement of Collateral Perfusion and Regional Function by Catheter-Based Implantation of Peripheral Blood Mononuclear Cells into Ischemic Hibernating Myocardium"Arterioscler Thromb Vasc Biol. 22. 1804-1810 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yang Z, Matsubara H, 他7名: "Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction."Circulation. 106. 106-111 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Amano K, Matsubara H, 他7人: "Enhancement of ischemia-induced angiogenesis by eNOS expression"Hypertension. 41:2. 156-162 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurisu S, Matsubara H, 他8人: "Cardiac angiotension II type 2receptor activates the kiniu/No system"Hypertension. 41:2. 99-107 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tateishi-yuyama E, Matsubara H, 他6人: "Therapeutic angiogenesis for patients with limb ischemia by antologous transplantation of bone marrow cells"Lancet. 360:18. 427-435 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iba O, Matsubara H, 他7人: "Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs"Circulation. 106:81. 2019-2025 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kamihata H, Matsubara H, 他6人: "Improvement of collateral perfusion and regional function by catheter-based implantation of peripheral blood cells"Arteriscler Thromb Vasc Biol. 22. 1804-1810 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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