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Gene transfer of angiogenic growth factor for treatment of chronic limb ischemia

Research Project

Project/Area Number 10671103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionThe University of Tokyo

Principal Investigator

OSHIRO Hidemi (2000)  The University of Tokyo Hospital, Vascular Surgery, Instructor, 医学部・附属病院, 助手 (80272558)

畠山 卓弥 (1998-1999)  東京大学, 医学部・附属病院, 助手 (60291324)

Co-Investigator(Kenkyū-buntansha) HAMADA Hirohumi  Sapporo Medical Univ, Molecular Medicine, Prof, 医学部・分子生物医学研究部門, 教授
MIYATA Tetsuro  The University of Tokyo Hospital, Vascular Surgery, Assistant Prof, 医学部・附属病院, 講師 (70190791)
SHIGEMATSU Hiroshi  The University of Tokyo Hospital, Vascular Surgery, Associate Prof, 医学部・附属病院, 助教授 (40134556)
大城 秀巳  東京大学, 医学部・附属病院, 助手 (80272558)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsAdenovirus / Basic FGF / Ex vivo gene transfer / Chronic ischemia / Collateral vessel / アデノウイルス / 血管新生 / 遺伝子組換え / 閉塞性動脈硬化症
Research Abstract

Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor(bFGF), a new strategy for the treatment of chronic vascular occlusive disease, was examined in a rabbit model of hind limb ischemia. The left femoral artery was completely excised to induce an ischemic state in the hind limb of male rabbits. Simultaneously, a skin section was resected from the wound, and host fibroblasts were cultured. The cultured fibroblasts were infected with adenovirus vector containing modified human bFGF cDNA with the secretory signal sequence(AxCAMAssFGF)or LacZ cDNA(AxCALacZ). At 21 days after femoral artery excision, the gene-transduced fibroblasts were administered through the left internal iliac artery. The fibroblasts significantly accumulated in the ischemic hind limb, and the AxCAMAssbFGF-treated cells secreted bFGF for less than 14 days without elevation of systemic bFGF level. At 28 days after cell administration, calf blood pressure ratio, angiographic score, capillary density of muscle tissue and blood flow of the left internal iliac artery were determined, and animals with AxCAMAssbFGF-treated cells showed significantly greater development of cellateral vessels, as compared to those with AxCALacZ-treated cells. These findings suggest that adenovirus-mediated ex vivo gene transfer of bFGF was effective for improvement of chronic limb ischemia.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] N. Ohara, H. Koyama, T Miyata etal: "Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia"Gone Thosay. 8(in press). ( 200)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N.Ohara, H.Koyama, T.Miyata, H.Hamada, S.Miyatake, M.Akimoto, H.Shigematsu: "Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia"Gene therapy. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Deguchi J: "Targeting endogenous platelet-derived growth factor B-chain by adenovirus-mediated gene transfer potently inhibits in vivo smooth muscle proliferation after arterial Inlury"Gene Therapy. 6. 956-965 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 重松 宏: "最近の血管外科の進歩"外科と治療. 81(10). 483-484 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 宮田 哲郎: "遺伝子導入法の血管外科への応用" 外科. 60. 1680-1684 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 宮田 哲郎: "バルーン障害後再狭窄に対するPDGF-Bを標的とした治療の可能性" 脈管学. 38. 813-816 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hamada H: "Apotosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to glioma cells : implication for gene therapy." Human Gene Therapy. 9(14). 1983-1993 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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