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Isolation and identification of tissue stem cell for clinical application

Research Project

Project/Area Number 17590350
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKYUSHU UNIVERCITY

Principal Investigator

OKANO Shinji (2006)  Kyushu University, Graduate School of Medical Sciences, Division of Pathophysiological and Experimental Pathology, Department of Pathology, Research associate, 大学院医学研究院, 非常勤助手 (10380429)

金 成豪 (2005)  九州大学, 大学院・医学研究院, 学術研究員 (60380630)

Co-Investigator(Kenkyū-buntansha) NAKAGAWA Kazunori  Kyushu University, Graduate School of Medical Sciences, Division of Pathophysiological and Experimental Pathology, Department of Pathology, Research associate, 大学院医学研究院, 講師 (50217668)
SUEISHI Katsuo  Kyushu University, Graduate School of Medical Sciences, Division of Pathophysiological and Experimental Pathology, Department of Pathology, Professor, 大学院医学研究院, 教授 (70108710)
YONEMITSU Yoshikazu  Chiba University, Graduate School of Medical Sciences, Department of Gene Therapy, Professor, 大学院医学研究院, 客員教授 (40315065)
岡野 慎士  九州大学, 大学院・医学研究院, 非常勤助手 (10380429)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsTissue stem cell / Cord blood / I11 liver・liver regeneration / Vasculogenisis / FLK-1細胞 / 肝組織再生 / LDL受容体欠損マウス / 臍帯血液 / 分化
Research Abstract

Although tissue stem cells contribute to regeneration of tissue and has therapeutic potentials for clinical application of regenerative medicine, the use of the cells has some concerns including low proliferating capacity and low transplantable capacity as compared with ES cells. This study also reveals that ciliary body-derived tissue stem cells have an potential ability to differentiate into neural cells due to cell-aggregation without cell-proliferation. To overcome these issues, we identified and isolated a novel cell population, Albumin(ALB)+a-smooth muscle actin(a-SMA)VEGFR2+ cells, which also expressed the ES cell-expressing markers, and we also found out that the cells could differentiate to a-SMA+ smooth muscle cells or CD31+ vascular endothelial cells in the presence of PDGF-BB and VEGF, and could differentiate to ALB+ hepatocytes or CK18+ bile duct cells in the presence of HGF and EGF in vitro. Moreover, we found out that the non-stimulated VEGFR2+ cells could differentiate to α-SMA+ smooth muscle cells or CD31+ vascular endothelial cells, and HGF+EGF-stimulated VEGFR2+ cells could differentiate to hepatocytes or bile duct cells in vivo, when the cells were inoculated into subcapsule of spleens in partial hepatectomized adult mice.
Furthermore, we identified and isolated a cord blood-derived cell population, CD45-CD133+CD34+VEGFR2+ cells, which could form colonies and differentiate to CD133-CD31+ vascular endothelial cells or α-SMA+ smooth muscle cells in the presence of VEGF, IGF, FGF-2,and/or PDGF-BB in vitro. In therapeutic cell transplantation for clinical setting, although there is a concern about rejection by sensitized allo-reactive memory T cells, the cord blood-derived CD45-VEGFR2+ cells has a potential source as endothelial progenitor cell (EPC), because we indicated that CCL2 was highly expressed in the ischemic muscular tissues using our murine limb ischemia models.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (7 results)

All 2006

All Journal Article (7 results)

  • [Journal Article] Critical roles of memory T cells and antidonor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice.2006

    • Author(s)
      Nagata S et al.
    • Journal Title

      Transplantation 82

      Pages: 689-698

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2-mediated therapeutic neovascularization : critical role of the inflammatory/arteriogenic pathway.2006

    • Author(s)
      Fujii T et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 26

      Pages: 2483-2489

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation.2006

    • Author(s)
      Kohno R et al.
    • Journal Title

      Brain Res. 1093

      Pages: 54-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Critical roles of memory T cells and atidonor immunoglobulin in rejection of allogeneic marrow cells in sensitized recipient mice.2006

    • Author(s)
      Nagata S et al.
    • Journal Title

      Transplantation 82

      Pages: 689-698

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nonendothelial mesenchymal cell-derived MCP-1 is required for FGF-2-mediated therapeutic neovascularization : critical role of the inflammatory/artheriogenic pathway.2006

    • Author(s)
      Fujii T et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 26

      Pages: 2483-2489

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A Free Radical Scavenger But Not FGF-2-mediated Angiogenic Therapy Rescues Myonephrophathic Metabolic Syndrome in Severe Hind Limb Ischemia.2006

    • Author(s)
      Kaneko K, et al.
    • Journal Title

      Am J Physiol Heart Circ Physiol (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Diabetic microangiopathy in ischemic limb is a disease of disturbance of the PDGF-BB/PKC axis, but not of impaired expression of angiogenic factors.2006

    • Author(s)
      Tanii M, et al.
    • Journal Title

      Circ Res 98(1)

      Pages: 55-62

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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