| Project/Area Number |
07457299
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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 | 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 |
KITAMURA Soichiro Nara Medical Univ., Dept.Surgery III,Professor, 医学部, 教授 (10028607)
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| Co-Investigator(Kenkyū-buntansha) |
UENO Satoshi Nara Medical Univ., Dept.Genetics, Associated Professor, 医学部, 助教授 (40184949)
NIWAYA Kazuo Nara Medical Univ., Dept.Surgery III,Assistant, 医学部, 助手 (30254501)
KOBAYASHI Syuichi Nara Medical Univ., Dept.Surgery III,Assistant, 医学部, 助手 (50201489)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | GENE TRANSFER / CELL TRANSPLANTATION / RETROVIRUS / ADENOVIRUS / TRANSCRIPTION FACTOR / FETAL CELLS / CELL CYCLE / 心筋細胞移植 |
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| Research Abstract |
Cardiac cell transplantation is the one potential treatment for acute or chronic heart failure with a significant loss of myocardium. Prerequisites for cellular transplantation to the heart to be successful include the followings : 1. formation of a new functional syncytium between grafted and host cardiomyocytes, 2. the number of grafted cells large enough to improve cardiac function, and 3. long-term graft survival. The transfer of a therapeutic gene into the cells to be grafted may possibly solve these obstacles. To begin with, we performed cell transplantation of the gene transferred fetal myocardial cells with recombinant plasmids, retroviruses, or adenoviruses coding beta-galactosidase. We found that adenovirus vector transduced the reporter gene into cultured cardiomyocytes without any damage, and that the grafted cardiac cells survived and expressed beta-gal for 12 weeks. The gap junctions were formed between the host cardiomyocytes and grafted cells. On the other hand, the plasmid vectors was little efficient for gene transfer, and the gene transferred grafted cells by the retroviruses could not form the gap junction in the host hearts. Candidates for gene transfer are the genes to make cardiomyocytes proliferate or to make embryonic cells differentiate into cardiomyocytes. However, the mechanisms of regulating the proliferation and differentiation of cardiomyocytes are unclear. We examined the expression patterns of cell cycle relating genes (Cyclin D1-3, Cyclin dependent kinase inhibitors (p15, p16, p21, p27, p57)) on P19 EC cells differentiating into cardiomyocytes under alpha MEM culture medium containing 1% DMSO.The results suggested that Cyclin D2 and p21 might play a role in induction of differentiation into cardiomyocytes. The function of p27 and p57 may be a strong inhibition of proliferation in process of differentiation into cardiomyocytes.
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