2005 Fiscal Year Final Research Report Summary
Development of selective induction system for functionally specified cardiomyocytes using embryonic stem cells
| Project/Area Number |
16390224
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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 | KYOTO UNIVERSITY |
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Principal Investigator |
YAMASHITA Jun Kyoto University, Institute for frontier medical sciences, Associate Professor, 再生医科学研究所, 助教授 (50335288)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Embryonic stem cells / Flk1 / cardiomyocytes / cardiac regeneration / pacemaker / progenitor cells / human ES cells |
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| Research Abstract |
Previously, we have established an embryonic stem (ES) cell differentiation system that can systematically induce cardiovascular cells from common progenitor cells that express Flk1, a vascular endothelial growth factor receptor. In this proposal, we have tried to selectively induce functionally specified cardiomyocytes, such as pacemaker cells and ventricular cells, using our ES cell system. 1)Effective induction method of cardiomyocyte differentiation : When Flk1^+ cell were cocultured on OP9 stroma cells, Flk1^+ cells could give rise to cardiomyocytes, as well as endothelial cells. Approximately 10-18% of ES-derived cells were αMHC-GFP^+ cardiomyocytes, which was more than 2-3 times higher in induction efficiency than that of the conventional embryoid body method. 2)Global analysis of cardiomyocyte differentiation process : Among intermediate stages of cardiomyocyte differentiation, Flk1^+/CXCR4^+/vascular endothelial cadherin^- (FCV) cells specifically possessed cardiac progenitor potentials. We purified undifferentiated ES cells, Flk1^+ mesoderm cells, FCV cardiac progenitor cells, and αMHC-GFP^+ cardiomyocytes, and then generated global gene profile during cardiomyocyte differentiation using DNA chip. 3)Induction of functionally specified cardiomyocytes : We confirmed that, in addition to ventricular myosin^+ cells, HCN4^+ pacemaker cells, and connexin40^+ Purkinje cells were observed in induced cardiomyocytes. 4)Cardiomyocyte differentiation from human ES cells : Our research project for cardiomyocyte differentiation using human ES cells has been approved by the ministry (MEXT) in Japan, and we have launched human ES cell culture in our laboratory. We have already succeeded in inducing spontaneously beating colonies from human ES cells.
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[Journal Article] Differentiation from embryonic stem cells to vascular wall cells under in vitro pulsatile flow loading.2005
Author(s)
Huang H, Nakayama Y, Qin K, Yamamoto K, Ando J, Yamashita J, Itoh H, Kanda K, Yaku H, Okamoto Y, Nemoto Y.
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Journal Title
J Artif Organ 8
Pages: 110-118
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Angiotensin II suppresses growth arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase (MAPK).2005
Author(s)
Saito T, Itoh H, Yamashita J, Doi K, Chun TH, Tanaka T, Inoue M, Masatsugu K, Fukunaga Y, Sawada N, Sakaguchi S, Arai H, Tojo K, Tajima N, Hosoya T, Nakao K.
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Journal Title
Regul Pept 127
Pages: 159-167
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Therapeutic potential of thiazolidinedinoes in activation of peroxisome proliferator-activated receptor gamma for monocyte recruitment and endothelial regeneration.2005
Author(s)
Tanaka T, Fukunaga Y, Itoh H, Doi K, Yamashita J, Chun TH, Inoue M, Masatsugu K, Saito T, Sawada N, Sakaguchi S, Arai H, Nakao K.
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Journal Title
Eur J Pharmacol 508
Pages: 255-265
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Roles of thromboxane A2 and prostacyclin in development of atherosclerosis in apoE-deficient mice.2004
Author(s)
Kobayashi T, Tahara Y, Matsumoto M, Iguchi M, Sano H, Maruyama T, Arai H, Oida H, Yurugi-Kobayashi T, Yamashita JK, etc
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Journal Title
J Clin Invest 114
Pages: 784-794
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Roles of thromboxane A2 and prostacyclin in development of atherosclerosis in apoE-deficient mice.2004
Author(s)
Kobayashi T, Tahara Y, Matsumoto M, Iguchi M, Sano H, Maruyama T, Arai H, Oida H, Yurugi-Kobayashi T, Yamashita JK, Katagiri H, Majima M, Yokode M, Kita T, Narumiya S.
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Journal Title
J Clin Invest. 114
Pages: 784-794
Description
「研究成果報告書概要(欧文)」より
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[Patent(Industrial Property Rights)] 細胞分化誘導法2005
Inventor(s)
中山泰秀, 黄海瑛, 安藤譲二, 山下潤, 伊藤裕, 神田圭一, 岡本吉弘, 根本泰
Industrial Property Rights Holder
国立循環器病センター総長, 株式会社ブリジストン
Industrial Property Number
2005-066683
Filing Date
2005-03-10
Description
「研究成果報告書概要(和文)」より
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