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THERAPEUTIC ANGIOGENESIS INDUCED BY AUTOLOGOUS BONE MARROW CELLS IMPLANTATION FOR THE TREATMENT OF ISCHEMIC DISEASES

Research Project

Project/Area Number 13671391
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionYamaguchi University

Principal Investigator

HAMANO Kimikazu  YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE PROFESSOR, 医学部, 教授 (60263787)

Co-Investigator(Kenkyū-buntansha) SUZUKI Kazuhiro  YAMAGUCHI UNIVERSITY HOSPITAL ASSISTANT, 医学部附属病院, 助手 (40335740)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordstherapeutic angiogenesis / ischemic / bone marrow cell / stem cell / blow flow / cell implantation / growth factor / survival / 細胞生存 / 心機能 / 投与経路
Research Abstract

Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear cells (BM-MNCs), but the best cell fraction in BM-MNCs and the best delivery road for inducing therapeutic angiogenesis kept unclear.
At first, we investigated the roles of stem cell fractions in BM-MNCs in this treatment. Stem cells were separated from mature BM-MNCs of mice using the antibody to stem cell receptor (CD117). More than ten-fold higher levels of VEGF were secreted from the CD117^+ cells than from the CD117^- cells (P< 0.001) 14 days after culture. Most of the CD117^- cells died, but the CD117^+ cells grew well and differentiated into endothelial ceils within 14 days of culture. CD117^+ cells (2 x 10^5), CD117^- cells (9.8 x 10^6), and total BM-MNCs (1 x 10^7) were also implanted into the ischemic hindlimbs of mice. The blood perfusion of the ischemic hindlimbs was significantly higher in the CD117^+ cell-implanted mice than in the CD117^- cell-implanted mice (P<0.01), but did not differ significantly from the BM-MNCs cell-implanted mice, 14 days after treatment. These results indicated that CD117^+ stem cells play a key role in the therapeutic angiogenesis induced by bone marrow cell implantation.
Then, we investigated the potency of therapeutic angiogenesis inducing by BM-MNCs using different delivery roads in an acute myocardium infarction model in rats. After the ligation of left ascending coronary artery, BM-MNCs (1 x 10^7) were given intramuscularly (IM group) or intravenously (IV group). The survival of BM-MNCs was better in the IM group than the IV group. Furthermore, both the blood flow of infarction area and the cardiac ejection fraction were significantly higher in the IM group than the IV group. These results indicated that the angiogenic potency inducing by BM-MNCs implantation was better by local intramuscularly injection than by intravenous delivery.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Nishida M, et al.: "Improvement of cardiac function by bone marrow cell implantation in a rat hypoperfusion heart model"The Annals of Thoracic Surgery. 75. 768-773 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata K, et al.: "Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model"American Journal of Physiology-Heart and Circulatory Physiology. 284. H66-H70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li TS, et al.: "Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats"American Journal of Physiology-Heart and Circulatory Physiology. 283. H468-H473 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi T, et al.: "Angiogenesis induced by the injection of peripheral leukocytes and platelets"Journal of Surgical Research. 103. 279-286 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamano K, et al.: "Therapeutic angiogenesis induced by local autologous bone marrow cell implantation"The Annals of Thoracic Surgery. 73. 1210-1215 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishida M., et al.: "Improvement of cardiac function by bone marrow cell implantation in a rat hypoperfusion heart model"Ann Thorac. Surg.. 75. 768-773 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata K., et al.: "Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model"Am J. Physiol. Heart Circ. Physiol.. 284. H66-70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li TS., et al.: "Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats"Am J. Physiol. Heart Circ. Physiol.. 283. H468-473 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi T., et al.: "Angiogenesis induced by the injection of peripheral leukocytes and platelets"J. Surg. Res.. 103. 279-286 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hamano K., et al.: "Therapeutic angiogenesis induced by local autologous bone marrow cell implantation"Ann. Thorac. Surg.. 73. 1210-1215 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishida M, et al.: "Improvement of cardiac function by bone marrow cell implantation in a rat hypoperfusion heart model"The Annals of Thoracic Surgery. 75. 768-773 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hirata K, et al.: "Autologous bone marrow cell implantation as therapeutic angiogenesis for isehemic hindlimb in diabetic rat model"American Journal of Physiology-Heart and Circulatory Physiology. 284. H66-H70 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Li TS, et al.: "Improved angiogenic potency by implantation of ex vivo hypoxia prestimulated bone marrow cells in rats"American Journal of Physiology-Heart and Circulatory Physiology. 283. H468-H473 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobayashi T, et al.: "Angiogenesis induced by the injection of peripheral leukocytes and platelets."Journal of Surgical Research. 103. 279-286 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamano K: "Therapeutic angiogenesis induced by local autologous bone marrow cell implantation"The Annals of Thoracic Surgery. 73(In Press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hamano K: "The induction of angiogenesis by the implantation of autologous bone marrow cells : a novel and simple therapeutic method."Surgery. 130(1). 44-54 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikenaga S: "Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model."Journal of Surgical Research. 96(2). 277-283 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hamano K: "Angiogenesis induced by the implantation of self-bone marrow cells : a new material for therapeutic angiogenesis."Cell Transplantation. 9(3). 439-443 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi T: "Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model."Journal of Surgical Research. 89(2). 189-195 (2000)

    • Related Report
      2001 Annual Research Report

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

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