2000 Fiscal Year Final Research Report Summary
Gene transfer of angiogenic growth factor for treatment of chronic limb ischemia
| Project/Area Number |
10671103
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OSHIRO Hidemi The University of Tokyo Hospital, Vascular Surgery, Instructor, 医学部・附属病院, 助手 (80272558)
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| 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)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Adenovirus / Basic FGF / Ex vivo gene transfer / Chronic ischemia / Collateral vessel |
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| 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.
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