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Therapeutic angiogenesis by cell transplantation

Research Project

Project/Area Number 13470150
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionShinshu University Graduate School of Medicine (2003)
Jichi Medical University (2001-2002)

Principal Investigator

IKEDA Uichi  Shinshu University Graduate School of Medicine, Department of Organ Regeneration, Professor, 大学院・医学研究科, 教授 (30221063)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Keiji  Shinshu University Graduate School of Medicine, Jichi Medical School, Assistant Professor, 医学部, 講師 (50245073)
NEGISHI Naoki  Shinshu University Graduate School of Medicine, Department of Organ Regeneration, Associate Professor, 大学院・医学研究科, 助教授 (30218268)
TAKAHASHI Masafumi  Shinshu University Graduate School of Medicine, Department of Organ Regeneration, Associate Professor, 大学院・医学研究科, 助教授 (40296108)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
Keywordsregeneration / atherosclerosis / myocardial infarction / bone marrow / 血管新生 / 幹細胞 / 遺伝子治療
Research Abstract

Recently, the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells (BM-MNCs) to ischemic limbs have been reported. We investigated whether transplantation of peripheral blood mononuclear cells (PB-MNCs) would also be as effective as BM-MNC-transplantation in patients with peripheral arterial disease. BM-MNC-transplantation into unilateral ischemic limbs was performed in five patients, and both BM-MNC and PB-MNC-transplantation into bilateral ischemic limbs (BM-MNCs into severe ischemic limbs and the same number of PB-MNCs into contralateral less ischemic limbs) were performed in five patients. The number of CD34^+ cells in PB-MNCs was 〜100-fold less than that in BM-MNCs, while PB-MNCs secreted substantial amounts of vascular endothelial growth factor (VEGF) during a 24-hour incubation. There was no increase in the serum VEGF levels by BM-MNC-transplantation alone, while there was a significant increase in the serum VEGF levels after transplantation of both BM-MNCs and PB-MNCs. Two weeks after transplantation, the ankle-brachial index and transcutaneous oxygen pressure were significantly increased in BM-MNC-transplanted limbs, while there were no significant increases in these parameters in PB-MNC-transplanted limbs.We demonstrate that autologous transplantation of BM-MNCs represents a new and promising strategy for clinical application designed to revascularize ischemic tissues, but there were no definite therapeutic effects of transplantation of PB-MNCs.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Matsui K, Ikeda U, et al.: "Intravenous prostaglandin E1 reduces monocyte chemoattractatn protein-1 levels in peripheral arterial disease."Am Heart J. 145. 330-333 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogata Y, Ikeda U, et al.: "Antiapoptotic effect of endothelin-1 in rat cardiac myocytes in vitro."Hypertension. 41. 1156-1163 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagata M, Ikeda U, et al.: "Efficinet gene transfer of a simian immnodeficiency viral vector into cardiomyocytes derived from primate embryonic stem cells."J Gene Med. 5. 921-928 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui K, Ikeda U, et al.: "Serum levels of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease."Circ J. 67. 660-662 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eizawa T, Ikeda U, et al.: "Circulating endothelial progenitor cells are reduced in hemodialysis patients."Curr Med Res Opin. 67. 627-633 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui K, Ikeda U, et al.: "Therapeutic angiogenesis by transplantation of autologous bone marrow and peripheral blood mononuclear cells in patients with peripheral arterial disease."Int J Angiol. 12. 155-161 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui K, Ikeda U, et al.: "Intravenous prostaglandin E1 reduces monocyte chemoattractant protein-1 levels in peripheral arterial disease."Am Heart J. 145. 330-333 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ogata Y, Ikeda U, et al.: "Antiapoptotic effect of endothelin-1 in rat cardiac myocytes in vitro."Hypertension. 41. 1156-1163 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nagata M, Ikeda U, et al.: "Efficinet gene transfer of a simian immnodeficiency viral vector into cardiomyocytes derived from primate embryonic stem cells."J Gene Med. 5. 921-928 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui K, Ikeda U, et al.: "Serum levels of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease."Cric J. 67. 660-662 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Eizawa T, Ikeda U, et al.: "Circulating endothelial progenitor cells are reduced in hemodialysis patients."Curr Med Res Opin. 19. 627-633 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui K, Ikeda U, et al.: "Therapeutic angiogenesis by transplantation of autologous bone marrow and peripheral blood mononuclear cells in patients with peripheral arterial disease."Int J Angiol. 12. 155-161 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsui K, Ikeda U, et al.: "Intravenous prostaglandin E1 reduces monocyte chemoattractatn protein-1 levels in peripheral arterial obstructive disease"Am.Heart J.. 145. 330-333 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogata Y, Ikeda U, et al.: "Antiapoptotic effect of endothelin-1 in rat cardiac myocytes in vitro"Hypertension. 41. 1156-1163 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nagata M, Ikeda U, et al.: "Efficient gene transfer of a simian immnodeficiency viral vector into cardiomyocytes derived from primate embryonic stem cells"J Gene Med. 5. 921-928 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsui K, Ikeda U, et al.: "Serum levels of vascular endothelial growth factor and monocyte-colony stimulating factor in peripheral arterial disease"Circ J. 67. 660-662 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Eizawa T, Ikeda U, et al.: "Circulating endothelial progenitor cells are reduced in hemodialysis patients"Curr Med Res Opin. 67. 627-633 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsui K, Ikeda U, et al.: "Therapeutic angiogenesis by transplantation of autologous bone marrow and peripheral blood mononuclear cells in patients with peripheral arterial disease"Int J Angiol. 12. 155-161 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hojo, Y., et al.: "Matrix metalloproteinase expression in the coronary circulation induced by coronary angioplasty"Atherosclerosis. 161. 185-192 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hojo, Y., et al.: "Increased levels of monocyte-related cytokines in patients with unstable angina"Atheroslerosis. 161. 403-408 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda, U., et al.: "C-reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes"Cardivasc. Res.. 56. 86-92 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito, T., et al.: "Regulation of interleukin-8 expression by HMG-CoA redyctase inhibitors in human vascular smooth uscle cells"Atheroslerosis. 165. 51-55 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimpo, M., et al.: "AAV-mediated VEGF gene transfer into skeletal muscle stimulates angiogenesis and improves blood flow in a rat hindlimb ischemia model"Cardivasc. Res.. 53. 993-1001 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tateishi-Yuyama E., et al.: "Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells"Lancet. 360. 427-435 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松井圭司他: "血管再生療法,造血幹細胞-基礎から遺伝子治療・再生医療へ(小澤敬也編)"中外医学社. 8 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikeda, U., et al.: "Interaction between monocytes and vascular endothelial cells induces adrenomedullin production"Atherosclerosis. 155. 381-387 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikeda, U., et al.: "The antiinflammatory effects of statins"N.Engl.J.Med.. 345. 1210-1211 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, K., et al.: "The site of mitral valve prolapse is a predictor of atrial fibrillation"Am.J.Cardiol.. 88. 811-813 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, K., et al.: "Peroxisome proliferator-activated receptor activators inhibit cardiac hypertrophy in cardiac myocytes"Circulation. 104. 1670-1675 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, M., et al.: "A novel mutation in exon 2 of the low density lipoprotein-receptor gene in a patient with homozygous familiar hypercholesterolemia"Clin.Genet.. 59. 290-292 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, M., et al.: "Macropahge migration inhibitory factor as a edox-sensitive cytokine in cardiac myocytes"Cardiovas.Res.. 52. 438-445 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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