| Project/Area Number |
14370234
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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 |
Circulatory organs internal medicine
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
IMAIZUMI Tsutomu Kurume University, School of Medicine, Professor, 医学部, 教授 (60148947)
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| Co-Investigator(Kenkyū-buntansha) |
KAI Hisashi Kurume University, School Of Medicine, Associate Professor, 医学部, 助教授 (60281531)
MUROHARA Toyoaki Nagoya University, School Of Medicine, Professor, 医学部, 教授 (90299503)
TAHARA Nobuhiro Kurume University, School Of Medicine, Assistant Professor, 医学部, 助手 (10320186)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | pulmonary hypertension / prostacyclin / gene therapy / stem cel / cell transplantation / macrophages / 肺高血圧 / レトロウイルス / STAT3 / 遺伝子治療 / レトロウイルスベクター |
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| Research Abstract |
(1)Naked plasmid encoding the prostacyclin synthase (PGIS) gene was injected into the thigh muscle every 7 days from 1 week and 4weeks after monocrotaline injection in rats. PGIS gene transfer increased intramuscular and serum 6-keto-prostaglandin F2-alpha, a stable metabolite of prostacyclin. Repeated PGIS gene transfers significantly reduced pulmonary arterial pressure and ameliorated right ventricular hypertrophy and pulmonary arterial remodeling in monocrotaline-treated rats. Furthermore, survival rate was significantly improved by repeated PGIS gene transfers.
(2)In normal rats, 3% of intravenously implanted bone marrow-derived mononuclear cells (BM-MNCs) accumulated in the lung 1 day after cell transplantation. Two weeks after cell transplantation, only 1 % of tranplnted BM-MNCs were detected in the lung. In contrast, the rate of lung distribution of transplanted BM-MNCs were remarkably increased in monocrotalin-induced pulmonary hypertension rats (10% and 6% at days 1 and 14, respectively).
(3)We established BM-MNC line, which overexpresses PGIS gene and produces prostacyclin, by using a retroviral vector-mediated gene transfer of PGIS.
(4)Transplantation of PGIS-overexpressing BM-MNCs significantly reduced pulmonary arterial pressure and ameliorated right ventricular hypertrophy in monocrotaline-induced pulmonary hypertension rats.
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