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Identification of vascular progenitor cells from monkey ES cells and application for cell implantation therapy with search for novel vascular inducing factor

Research Project

Project/Area Number 13557064
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Circulatory organs internal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

ITOH Hiroshi  Kyoto University Graduate School of Medicine, Department of Medicine and Clinical Science, Associate Professor, 医学研究科, 助教授 (40252457)

Co-Investigator(Kenkyū-buntansha) NITO Shinji  Tanabe Seiyaku Co., Ltd., Department of Advanced Medical Research, Discovery Research Laboratory, Senior Scientist, 創薬研究所・先端医学ユニット, 主任研究員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsregeneration medicine / ES cells / VEGF / primate / endothelial cells / vascular smooth muscle cells / DNA microarray / Flk-1 / 血管再生
Research Abstract

ES cells with totipotency and self-renewal attract many investigators' attention as promising cell sources for regeneration medicine. We previously reported that Flk-1, one of VEGF receptors, -positive cells derived from mouse ES cells can be differentiated into endothelial cells and vascular smooth muscle cells (VSMC) to construct blood vessels in vitro and named them as "vascular progenitor cells (VPC)". In this research, to aim at clinical application of ES cells-derived VPC to vascular regeneration medicine, we identified VPC in monkey ES cells. Undifferentiated monkey ES cells express Flk-1, unlike mouse ES cells. Differentiation of Flk-1 cells on collagen IV-coated dishes with VEGF induced Flk-1 +, alkaline phosphatase - cells, which can be differentiated into endothelial cells ad VSMC to construct blood vessel structures. We also examined the usefulness of ES cells-derived VPC for implantation to regenerate blood vessels in vivo. Implanted VPC differentiated with VEGF and serum in tumor angiogenesis model effectively contributed to neoangiogenesis and significantly augmented local blood flow, which suggests potentials of therapeutic application of ES cells-derived VPC.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Sone M, et al.: "Different differentiation kinetics of vascular progenitor cells in primate and mouse embryonic stem cells"Circulation. 107. 2085-2088 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyashita K, et al.: "Adrenomedullin promotes proliferation and migration of cultured endothelial cells"Hypertens. Res.. 26. S93-S98 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamahara K, et al.: "Significance and therapeutic potential of natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration"Proc. Natl. Acad. Sci. USA. 100. 3404-3409 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masatsugu K, et al.: "Shear stress attenuates endothelin and endothelin converting enzyme expression through oxidative stress"Regulatory Peptide. 111. 13-19 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kook H, et al.: "Physiological concentration of atrial natriuretic peptide induces endothelial regeneration in vitro"Am. J. Physiol.. 284. H1388-H1397 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yurugi-Kobayashi T, et al.: "Contribution of transplanted vascular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage"Blood. 101. 2675-2678 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohno N, et al.: "Accelerated re-endothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide"Circulation. 105. 1623-1626 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamahara K, et al.: "New diagnostic procedure for primary aldosteronism : Adrenal venous sampling under adrenocorticotropic hormone and angiotensin II receptor blocker -Application to a case of bilateral multiple adrenal microadenomas"Hypertens. Res.. 24. 145-152 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito T, et al.: "Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells"Am. J. Physiol.. 281. H1364-H1371 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chusho H, et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide"Proc. Natl. Acad. Sci. USA. 98. 4016-4021 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Doi K, et al.: "C-type natriuretic peptide induces re-differentiation of vascular smooth muscle cells with accelerated re-endothelialization"Arterioscler. Thromb. Vasc. Biol.. 21. 930-936 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukunaga Y, et al.: "Thiazolidinediones, peroxisome proliferator-activated receptor γ agonists, regulate endothelial cell growth and secretion of vasoactive peptides"Atherosclerosis. 158. 113-119 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue M, et al.: "Oxidized low density lipoprotein regulates VEGF expression in human macrophages and endothelial cells through activation of PPAR γ"Arterioscler. Thromb. Vasc. Biol.. 21. 560-566 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sawada N, et al.: "cGMP-dependent protein kinase phosphorylated and inactivates RhoA"Biochem. Biophys. Res. Commun.. 280. 798-805 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Sone, et al.: "Different differentiation kinetics of vascular progenitor cells in primate and mouse embryonic stem cells"Circulation. 107. 2085-2088 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Miyashita, et al.: "Adrenomedullin promotes proliferation and migration of cultured endothelial cells"Hypertens. Res.. 26. S93-S98 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Yamahara, et al.: "Significance and therapeutic potential of natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration"Proc. Natl. Acad. Sci. USA. 100. 3404-3409 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Masatsugu, et al.: "Shear stress attenuates endothelin and endothelin converting enzyme expression through oxidative stress"Regul. Pept.. 111. 13-19 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Kook, et al.: "Physiological concentration of atrial natriuretic peptide induces endothelial regeneration in vitro"Am. J. Physiol.. 284. H1388-1397 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Yurugi-Kobayashi, et al.: "Contribution of transplanted vaseular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage"Blood. 101. 2675-2678 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Ohno, et al.: "Accelerated re-endothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide"Circulation. 105. 1623-1626 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K Yamahara, et al.: "New diagnostic procedure for primary aldosteronism: Adrenal venous sampling under adrenocorticotropic hormone and angiotensin II receptor blocker - Application to a case of bilateral multiple adrenal microadenomas"Hypertens. Res.. 25. 145-152 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Saito, et al.: "Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells"Am. J. Physiol.. 281. H1364-H1371 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H. Chusho, et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide"Proc. Natl. Acad. Sci. USA. 98. 4016-4021 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Doi, et al.: "C-type natriuretic peptide induces re-differentiation of vascular smooth muscle cells with accelerated re-endothelialization"Arterioscler. Thromb. Vasc. Biol.. 21. 930-936 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Fukunaga, et al.: "Thiazolidinediones, peroxisome proliferator-activated receptor γ agonists, regulate endothelial cell growth and secretion of vasoactive peptides"Atherosclerosis. 158. 113-119 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Inoue, et al.: "Oxidized low density lipoprotein regulates VEGF expression in human macrophages and endothelial cells through activation of PPAR γ"Arterioscler. Thromb. Vasc. Biol.. 21. 560-566 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Sawada, et al.: "cGMP-dependent protein kinase phosphorylated and inactivates RhoA"Biochem. Biophys. Res. Commun.. 280. 798-805 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamahara K, et al.: "New diagnostic procedure for primary aldosteronism : Adrenal venous sampling under adrenocorticotropic hormone and angiotensin II receptor blocker -Application to a case of bilateral multiple adrenal microadenomas"Hypertens.Res.. 24. 145-152 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohno N, et al.: "Accelerated re-endothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide"Circulation. 105. 1623-1626 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yurugi-Kobayashi T, et al.: "Contribution of transplanted vascular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage"Blood. 101. 2675-2678 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kook H, et al.: "Physiological concentration of atrial natriuretic peptide induces endothelial regeneration in vitro"Am.J.Physiol.. 284. H1388-H1397 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masatsugu K, et al.: "Shear stress attenuates endothelin and endothelin converting enzyme expression through oxidative stress"Regulatory Peptide. 111. 13-19 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamahara K, et al.: "Significance and therapeutic potential of natriuretic peptides/cGMP/cGMP-dependent protein kinase pathway in vascular regeneration"Proc.Natl.Acad.Sci. USA. 100. 3404-3409 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyashita K, et al.: "Adrenomedullin promotes proliferation and migration of cultured endothelial cells"Hypertens.Res.. 26. S93-S98 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sone M, et al.: "Different differentiation kinetics of vascular progenitor cells in primate and mouse embryonic stem cells"Circulation. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Sawada et al.: "cGMP-dependent protein kinase phosphorylated and inactivates RhoA"Biochem.Biophys.Res.Commun.. 280. 798-805 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Inoue et al.: "Oxidized low density lipoprotein regulates VEGF expression in human macrophages and endothelial cells through activation of PPARγ"Arterioscler.Thromb.Vasc.Biol.. 21. 560-566 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Fukunaga et al.: "Thiazolidinediones, peroxisome proliferator-activated receptor γ agonists, regulate endothelial cell growth and secretion of vasoactive peptides"Arterioscler.Thromb.Vasc.Biol.. 158. 113-119 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] k.Doi et al.: "C-type natriuretic peptide induces re-differentiation of vascular smooth muscle cells with accelerated re-endothelialization"Arterioscler.Thromb.Vasc.Biol.. 21. 930-936 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Chusho et al.: "Dwarfism and early death in mice lacking C-type natriuretic peptide"Proc. Natl.Acad.USA. 98. 4016-4021 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Saito et al.: "Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells"Am.J.Physiol.. 281. H1364-H1371 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] N.Ohno et al.: "Accelerated re-endothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide"Circulation. (in press). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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