1998 Fiscal Year Final Research Report Summary
Ex vivo gene transferred cardiomyocyte transplantation to heart failure
| Project/Area Number |
09307029
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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 | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Nara Medical University |
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Principal Investigator |
MIZUGUCHI Kazumi Nara Medical University, Department of Medicine, Assistant-Professor, 医学部, 講師 (80201789)
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| Co-Investigator(Kenkyū-buntansha) |
KITAMURA Soichiro National Cardiovascular Center, Vice-Director of a hospital, 国立循環器病センター, 副院長 (10028607)
TANIGUCHI Shigeki Nara Medical University, Department of Medicine, Professor, 医学部, 教授 (90183467)
TAKAKI Miyako Nara Medical University, Department of Medicine, Professor, 医学部, 教授 (00033358)
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| Project Period (FY) |
1997 – 1998
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| Keywords | cell transplantation / heart transplantation / gene transfer / gene gun / xenotransplantation / cross-circulation model / conductance catheter / appreciation of rat heart function |
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| Research Abstract |
1) We attempted to allogenic transplantation of swine fetal cardiomyocytes. But transplantation was unsuccessful due to allogenic reactivity after transplantation. Now, we examined immunosuppressive gene transfer to the donor cardiomyocytes and some means of gene transfer to cardiomyocytes. 2) To examine the means to change the allo- or xeno-reactivity after transplantation, we performed ex vivo transfer of marker gene to heart grafts using adenovirus vector. Successful gene transfer and expression of beta-gal gene were demonstrated. This result demonstrated that cardiomyocytes of the grafts expressed an exogenous gene products by adenovirusmediated gene transfer under hypothermic preservation condition. 3) We found that gene gun-mediated transfer of the EBV-based episomal vector into rat hearts results in long-lasting expression of a marker gene. Combined use of the gene gun and EBV-based episomal vector may contribute to gene therapy of cardiovascular diseases. To our knowledge, this
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is the first study showing that in vivo gene transfer into heart can be achieved using a gene gun. 4) We transfected rodent cells with EBV-episomal vectors carrying E.coli b-galactosidase gene as a marker gene. Significantly higher transient expression was demonstrated, both in vivo and in vitro, in rodent cells transfected with the EBV vector compared to the cells transfected with a conventional vector. 5) We transplanted porcine cryopreserved aortic valve to dog aorta for the purpose of assessment of the ability of discordant xeno-tissue-transplantation. Compared with fresh tissue, cryopreserved valves kept cell viability. This result suggests the ability of clinical use. 6) We instituted a miniaturized six-electrode conductance catheter for rat LV volume measurement and LV pressure was simultaneously measured with a 3-F catheter-tip micromanometer introduced into the LV through the apex. Using these two catheters, we could appreciate rat heart function successfully. 7) We attempted to propose a novel method to assess oxygen cost of LV contractility from the curved ESPVRs in the rat heart. We succeeded in obtaining oxygen cost of LV contractility Less
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Research Products
(22 results)
