1997 Fiscal Year Final Research Report Summary
Adenovirus-mediated gene therapy for cerebrovascular disorders
| Project/Area Number |
08671575
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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 |
Cerebral neurosurgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAGATA Izumi Department of Neurosurgery, Kyoto University. Associate professor, 医学研究科, 講師 (10198327)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATAKE Shin-Ichi Department of Neurosurgery, Kyoto University. Associate professor, 医学研究科, 講師 (90209916)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Adenovirus / Angiogenesis / Basic fibroblast growth factor / Endothelial cells / Gene transfer |
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| Research Abstract |
To investigate the possibility of adenovirus-mediated gene transfer in the treatment of vascular occulusive diseases, we constructed a replication-deficient recombinant adenovirus vector coding for human basic fibroblast growth factor (bFGF) and examined its effect on the proliferation and differentiation of vascular endothelial cells in vitro. Human umbirical vein endothelial cells (HUVECs) were successfully infected with high efficiency, and expressed 18 kD protein which is immunoreactive to anti-bFGF monoclonal antibody. This protein was accumulated mainly in the nuclei of the cells, but was also detected in the culture medium although the complimentary DNA (cDNA) did not contain the classical secreting signal sequence. The proliferation assay of HUVECs infected with bFGF-expressing adenovirus revealed a significant increase in cell number over control. Infection with this virus also enhanced tubular formation of HUVECs on reconstituted basement membrane. Neovascularization and the formation of collateral vessels play important roles in minimizing tissue damage in ischemic disorders. These results imply that the use of bFGF-expressing recombinant adenovirus may be a suitable in vivo-gene therapy for ischemic diseases.
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