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

血管生成生长因子的基因转移治疗慢性肢体缺血

• 批准号: 10671103
• 负责人: OSHIRO Hidemi
• 金额: $ 2.05万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671103/
• 关键词: Adenovirus; 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

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.

腺病毒介导的碱性成纤维细胞生长因子（BFGF）的离体基因转移（BFGF）是一种治疗慢性血管闭塞疾病的新策略，在后肢缺血的兔模型中检查了。完全切除左股动脉，以在雄性兔子的后肢诱导缺血状态。同时，从伤口切除了皮肤段，并培养了宿主成纤维​​细胞。培养的成纤维细胞被腺病毒载体感染，其中包含具有分泌信号序列（AxcamassFGF）或LACZ cDNA（Axcalacz）的修饰的人BFGF cDNA。在股动脉切除后21天，基因转导的成纤维细胞通过左侧动脉施用。成纤维细胞在缺血性后肢中显着积累，轴CamassBFGF处理的细胞分泌BFGF不到14天，而无需升高全身性BFGF水平。在细胞给药后28天，确定了小腿血压比，血管造影评分，肌肉组织的毛细血管密度和左内动脉的血液流动，并且与Axcalacz-Treated细胞相比，具有AxcamassBFGF细胞的动物表现出明显更大的细胞发育。这些发现表明，腺病毒介导的BFGF的离体基因转移有效改善慢性肢体缺血。

项目成果

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)

N. Ohara、H. Koyama、T Miyata 等人：“腺病毒介导的碱性成纤维细胞生长因子的离体基因转移促进兔后肢缺血模型的侧支发育”Gone Thosay。

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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). (200

N.Ohara、H.Koyama、T.Miyata、H.Hamada、S.Miyatake、M.Akimoto、H.Shigematsu：“腺病毒介导的碱性成纤维细胞生长因子的离体基因转移促进兔后脑模型的侧支发育

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