| Project/Area Number |
17209029
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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 |
Circulatory organs internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
FUKUDA Keiichi Keio University, School of Medicine, Professor (20199227)
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| Co-Investigator(Kenkyū-buntansha) |
MURATA Mitsushige Keio University, School of Medicine, Instructor (30317135)
YUASA Shinsuke Keio University, School of Medicine, Instructor (90398628)
HATTORI Fumiyuki Keio University, School of Medicine, Researcher (50398624)
TANIOKA Yoshikuni Central Institute for Experimental Animals, Animal Experimentation Center, Researcher(non-tenuerd) (10072406)
SASAKI Erika Central Institute for Experimental Animals, Animal Experimentation Center, Researcher(non-tenuerd) (70390739)
吉岡 正豊 慶應義塾大学, 医学部, 嘱託(非常勤) (30398630)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥49,530,000 (Direct Cost: ¥38,100,000、Indirect Cost: ¥11,430,000)
Fiscal Year 2007: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2006: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2005: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
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| Keywords | human embryonic stem cell / common marmosset / Regeneratie Medicine / Cardiomyocyte / differentiation / Development / Noggin / Cell Transplantation / 胚性幹細胞 / 奇形腫 / 多分化能 / 転写因子 / NKX2.5 / イオンチャネル / 心筋梗塞 |
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| Research Abstract |
This Study tried to establish a novel method for generation, purification, and transplantation of new cardiomyocytes from human and common marmoset ES cells. We found that Noggin induce differentiation from ES cells to antero-lateral mesodermal cell, and that factor X promote differentiation from antero-lateral mesodermal cells to cardiomyocytes. Moreover, we found that Y-receptor is strongly expressed at the early differentiated cardiomyocytes, and administration of Y ligand promoted cell division in embryonic cardiomyocyte in vivo and early differentiated cardiomyocytes from ES cells. In combination with these factors, we can produce cardiomyocytes from marmoset and human ES cells. We also developed a novel method to purify cardiomyocytes from the mixture of cells by using mitochondria-specific incorporated dye. We transplanted the cardiomyocytes purified by this method, and the grafted cardiomyocytes can eliminate teratoma formation. Moreover, we also developed a novel method to enhance the cell survival after transplantation by a re-aggregation method. The grafted cell survival by needle injection into the heart was less than 1%, while this method can improve the efficiency up to 90%. We transplanted the purified cardiomyocytes into immuno-deficient mouse and common marmoset monkeys, In combination with these various techniques, we developed an efficient method to purify cardiomyocytes.
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