• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Novel angiogenic gene therapy for the treatment of ischemic limb

Research Project

Project/Area Number 13557098
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General surgery
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

MIYATA Tetsuro  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (70190791)

Co-Investigator(Kenkyū-buntansha) 濱田 洋文  札幌医科大学, 医学部, 教授 (00189614)
KOYAMA Hiroyuki  The University of Tokyo, Faculty of Medicine, visiting Associate Professor, 医学部附属病院, 客員助教授 (10241994)
SHIGEMATSU Hiroshi  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (40134556)
北川 剛  東京大学, 医学部・附属病院, 助手 (90262021)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥4,100,000 (Direct Cost: ¥4,100,000)
KeywordsAngiogenic therapy / bFGF / VEGF / Ephrin B2 / Rabbit / Gene therapy / Ex vivo / Eph B4 / CD40リガンド / ウサギ / ポリエチレンイミン / Therapeutic angiogenesis / Ephrine B2 / 血管新生 / ラテンウイエルス / Ex vivo / ラビット / 虚血肢
Research Abstract

Previously, we developed novel angiogenic therapy for the treatment of ischemic limbs, in which auto-fibroblasts, adenoviraIly transduced with modified bFGF gene, were infused into the ischemic limb thorugh an intra-arterial catheter (ex vivo method). In the present study, we determined (1)how many gene-transduced fibroblasts induced appropriate therapeutic effects and (2)which angiogenic growth factor effectively promoted the development of collateral vessels (VEGF vs bFGF).
1.Appropriate control of the ex vivo gene therapyWe injected various numbers of gene (bFGF)-transduced fibroblasts (5x10^5 cells, 1x 10^6 cells, 5x10^6 cells and 1x10^7 cells) to the rabbit model of hind limb ischemia, and evaluated angiogenic effects at 28 days after intra-arterial administration. There were no significant effects in the rabbits treated with 5x10^5 cells nor 1x 10^6 cells. In the animals treated with 5x10^6 cells or 1x10^7 cells significant improvement of tissue perfusion was observed, though abundant cells were distributed to lung after injection of 1x10^7 cells. These findings indicated that 5x10^6 was appropriate number of cell administration.
2.VEGF vs bFGF
The auto-fibroblasts, which were transferred with VEGF gene (VEGF group) or bFGF gene (bFGF group), were injected to rabbit ischemic limb in the same manner. Twenty-eight days after the treatment, collateral conductance and angiographic score in the bFGF group was significantly higher than those in the VEGF group, while no significant difference was detected in calf blood pressure ratio and capillary density between the bFGF and VEGF groups. These data suggested that bFGF promoted arteriogenesis as compared with VEGF.

Report

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

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Ohara N, Miyata T et al.: "Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia"Gene Therapy. 8. 837-845 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ninomiya M, Miyata T et al.: "Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model"Gene therapy. 10. 1152-1160 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T et al.: "Long-term survival after surgical treatment of patients with Takayasu's arteritis."Circulation. 108. 1474-1480 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondoh K, Miyata T et al.: "Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor."Cardiovascular Research. 61. 132-142 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii S, Miyata T et al.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia."Journal of Vascular Surgery. 39. 629-638 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohara N, Koyama H, MiyataT, Harnada H, Miyatake S, Shigematsu H.: "Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia"Gene Therapy. 8. 837-845 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ninomiya M, Koyama H, Miyata T, Hamada H, Miyatake S, Shigematsu H, Takamoto s.: "Ex vivo gene transfer of basic fibroblast growth factor improves cardiac function and blood flow in a swine chronic myocardial ischemia model."Gene Therapy. 10. 1152-1160 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T, Sato 0, Koyama H, Shigernatsu H, Tada Y.: "Long-term survival after surgical treatment of patients with Takayasu's arteritis."Circulation. 108. 1474-1480 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondoh K, Koyama H, Miyata T, Takato T, Hamada H, Shigematsu H.: "Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor."Cardiovascular Research. 61. 132-142 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ishii S, Koyama H, Miyata T, Nishikage S, Hamada H, Miyatake S, Shigematsu H.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia."J of Vascular Surgery. 39. 629-638 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikage S, Koyama H, Miyata T, Ishii S, Hamada H, Shigematsu H.: "In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb"J of Surgical Research.. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T, Shigematsu H et al.: "Long-term survival after surgical treatment of patients with Takayasu's arteritis"Circulation. 108. 1474-1480 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kondou K, Koyama H et al.: "Conduction Performance of Collateral Vessels Induced by Vascular Endothelial Growth Factor or Basic Fibroblast Growth Factor"Cardiovascular Research. 61. 132-142 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishii S, Koyama H et al.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels in rabbit model of hind limb ischemia"Journal of Vascular Surgery. 39. 629-638 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishikage S, Koyama H et al.: "In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb"Journal of Surgical Research. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ninomiya N, Koyama H, Miyata T, Shigematsu H et al.: "Exvivo gene transfer of basic fibroblast growth factor improves cardiac function"Gene Therapy. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮田哲郎, 小山博之: "血管の再生医療"呼吸と循環. 50(4). 377-383 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 宮田哲郎, 小山博之: "Adenovirus vectorを用いたbFGF遺伝子のex vivo導入による血管新生治療"脈管学. 42(6). 391-396 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小山博之, 宮田哲郎: "Ex vivo遺伝子導入法による新しい治療的血管新生療法の有効性と特性"脈管学. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小山博之: "血管新生療法の現状と将来展望"Progress in Medicine. 22(12). 3070-3076 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 小山博之, 重松宏: "血管外科における遺伝子治療の現状と将来展望"血管医学. 4(1). 73-79 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Inoue S, Kayama H, Miyata T, Shigematsu H: "Cell replication induces in stent lesion growth in rabbit carotid artery with preexisting intimal hyperplasia"Atherosclerosis. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 宮田哲郎, 小山博之, 大原伸介, 濱田洋文, 大城秀巳, 重松宏: "Adenovirus vectorを用いたbFGF遺伝子のex vivo導入による血管新生治療"脈管学. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohara N, Koyama H, Miyata T, Hamada H, Shigematsu H, et al.: "Adenovirus-mediated ex vivo gene transfer of basic fibroblust growth factor promotos collateral davelopment in a rabbit mode of"Gene Therapy. 8. 837-845 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue S, Koyama H, Miyata T, Shigematsu H: "Pathogenetic hererogeneity of in-stent lesion formation in human peripheial arterial disease"Journal of Vasalar Surgery. (in press).

    • Related Report
      2001 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi