2003 Fiscal Year Final Research Report Summary
Novel angiogenic gene therapy for the treatment of ischemic limb
| Project/Area Number |
13557098
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
MIYATA Tetsuro The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (70190791)
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| 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)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Angiogenic therapy / bFGF / VEGF / Ephrin B2 / Rabbit / Gene therapy / Ex vivo |
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| 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.
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