| Project/Area Number |
08557068
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 Tokyo Uni., Surgery, Lecturer, 医学部・附属病院, 講師 (70190791)
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| Co-Investigator(Kenkyū-buntansha) |
TAKUWA You Kanazawa Uni., Physiology, Professor, 医学部, 教授 (60171592)
HAMADA Hirofumi Cancer Institute, virology, Director, 化学療法センター・分子生物治療研究部, 部長 (00189614)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | small caliber vascular prosthesis / hybrid-type vascular prosthesis / endothelial cell / thrombomodulin / plasminogen activators / tissue plasminegen activator / thrombomonodulin / 遺伝子治療 / adenovirus / 血管内皮細胞 / 小口径人工血管 / PDGF |
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| Research Abstract |
Seeding of prosthetic grafts with genetically engineered vascular endothelial cells (ECs) provides the potential to enhance its antithromboticity. The retention of adenovirally htPA-transduced ECs seeded on expanded polytetrafluoloethylene (ePTFE) grafts and the function of tPA secretion in the canine model was examined. Our results suggest that overexpressed tPA makes little effect on the retention of seeded ECs in a short period. Shorter ex-vivo culture periods is the advantage to the in vivo retention of the ECs on the prosthesis.
Introduction of the human thrombomodulin gene to the ECs could greatly enhance the antithrombotic activity of the cells in vitro. However, ePTFE grafts seeded with this genetically modified ECs, when transplanted to the external iliac vein of monkey, failed to show the superior patency over the control grafts. Now the system which enable to evaluate the in-vivo function of the genetically modified ECs is developing to exclude the technical problem accompanying the graft implantation.
Introduction of the basic fibroblast growth factor (bFGF) gene to fibroblasts and seeding the cells to the ischemic limb in the rabbi, could enhance the angiogenesis in the limb. This method could be lead to the development of a new strategy of treatment of the ischemic limb.
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