2004 Fiscal Year Final Research Report Summary
Application of human ES-derived vascular progenitor cells to elucidation of vascular development/differentiation and vascular regeneration medicine
| Project/Area Number |
15209028
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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 | Kyoto University |
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Principal Investigator |
ITOH Hiroshi Kyoto University, Department of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (40252457)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Jun Kyoto University, Institute for Frontier Medical Sciences, Associate Professor, 再生医科学研究所, 助教授 (50335288)
NAKAYAMA Yasuhide National Cardiovascular Center, Department of Biomedical Engineering, Laboratory Chief, 室長 (50250262)
NITO Shinji Tanabe Seiyaku Co., Ltd., Discovery Research Laboratory, Department Manager, 創薬研究所, 主任研究員
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| Project Period (FY) |
2003 – 2004
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| Keywords | human ES cells / regeneration medicine / progenitor cells / endothelial cells / vascular smooth muscle cells / VEGF / natriuretic peptides / adrenomedullin |
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| Research Abstract |
From human ES cells we identified and isolated "vascular progenitor cells;VPC", which can be differentiated into both endothelial cells(EC) and vascular smooth muscle cells(VSMC) and organize blood vessel structure in vitro. Human ES cell-derived VPC(hESC-VPC) are TRA-1-Flk1+VEcadherin-PDGFR+ cells. We also discovered that vasodilating peptides, natriuretic peptides and adrenomedullin(AM) can activate cGMP and cAMP cascade, respectively and promote vascular regeneration, by several gene-engineered mice for these peptides, which we developed and by adenovirus-mediated gene transfer technique. Furthermore, we demonstrated that AM potently induces endothelial differentiation of mouse ES cell-derived VPC. Transplantation of EC and VSMC at early differentiation stage induced construction of human blood vessels in vivo and enhanced local blood flow to exert therapeutic effectiveness in hindlimb ischemia model or skin ulcer model. By in vitro human vascular development system, using human VPC, we elucidated the gene expression profiling of human undifferentiated ES,VPC and EC or SMC at early differentiation stage. Furthermore, we developed new biomaterial for blood vessel walls and seeded ES cell-derived VPC onto it. VPC in the artificial blood vessel walls were demonstrated to be differentiated into EC and VSMC by pulsatile flow loading.
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[Journal Article] Therapeutic potential of thiazolidinediones in activation of peroxisome proliferators-activated receptor γ for monocyte recruitment and endothelial regeneration.2005
Author(s)
T.Tanaka, Y.Fukunaga, H.Itoh, K.Doi, J.Yamashita, T-H.Chun, M.Inoue, K.Masatsugu, T.Saito, N.Sawada, S.Sakaguchi, H.Arai, K.Nakao
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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] Angiotensin II suppresses growth-arrest specific homeobox (Gax) expression via redox-sensitive mitogen-activated protein kinase(MAPK).2005
Author(s)
T.Saito, H.Itoh, J.Yamashita, K.Doi, T-H.Chun, T.Tanaka, M.Inoue, K.Masatsugu, Y.Fukunaga, N.Sawada, S.Sakaguchi, H.Arai, K.Tojo, N.Tajima, T.Hosoya, K.Nakao
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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] Analysis of rat insulin n promoter-ghrelin transgenic mice and rat glucagons promoter-ghrelin transgenic mice.2005
Author(s)
H.Iwakura, K.Hosoda, C.Son, J.Fujikura, T.Tomita, M.Noguchi, H.Ariyasu, K.Takaya, H.Masuzaki, Y.Ogawa, T.Hayashi, G.Inoue, T.Akamizu, H.Hosoda, M.Kojima, H.Itoh, S.Toyokuni, K.Kangawa, K.Nakao
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Journal Title
J.Biol.Chem. 280
Pages: 15247-15256
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Shear stress attenuates endothelin and endothelin converting enzyme expression through oxidative stress.2003
Author(s)
K.Masatsugu, H.Itoh, T-H.Chun, T.Saito, J.Yamashita, K.Doi, M.Inoue, N.Sawada, Y.Fukunaga, S.Sakaguchi, M.Sone, K.Yamahara, T.Yurugi, K.Nakao
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Journal Title
Regulatory Peptides 111
Pages: 13-19
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Significance and therapeutic potential of natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration.2003
Author(s)
K.Yamahara, H.Itoh, T-H.Chun, Y.Ogawa, J.Yamashita, N.Sawada, Y.Fukunaga, M.Sone, T.Yurugi-Kobayashi, K.Miyashita, H.Tsujimoto, H.Kook, R.Feil, D.L.Garbers, F.Hofmann, K.Nakao
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Journal Title
Proc.Natl.Acad.Sci.USA 100
Pages: 3404-3409
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Different differentiation kinetics of vascular progenitor cells in primate and mouse embryonic stem cells.2003
Author(s)
M.Sone, H.Itoh, J.Yamashita, T.Yurugi-Kobayashi, Y.Suzuki, Y.Kondo, A.Nonoguchi, N.Sawada, K.Yamahara, K.Miyashita, K.Park, S.Nito, M.Shibuya, S-I.Nishikawa, K.Nakao
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Journal Title
Circulation 107
Pages: 2085-2088
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, ブリヂストン
Industrial Property Number
特願2005-066683号
Filing Date
2005-03-10
Description
「研究成果報告書概要(和文)」より
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