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Generation of iPS cells from PAI-1 deficient patient and differentiation into mature cells

Research Project

Project/Area Number 24591420
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SANO Hideto  浜松医科大学, 医学部, 助教 (80623842)

Co-Investigator(Kenkyū-buntansha) URANO Tetsumei  浜松医科大学, 医学部, 教授 (50193967)
SUZUKI Yuko  浜松医科大学, 医学部, 准教授 (20345812)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsPAI-1 / iPS cells / endothelial cells / angiogenesis / 凝固・線溶 / iPS細胞 / 内皮細胞 / 血管新生 / 細胞接着 / 発生・分化 / 脂肪細胞 / 血球細胞
Outline of Final Research Achievements

We have identified two independent PAI-1 deficient patients having apparent phenotypes of severe bleeding and impaired wound healing, both of which are not seen in the PAI-1 deficient mice. To investigate the intrinsic function of PAI-1 in different cell types, iPS cells from the patients were generated, and their phenotypes have been analyzed after being differentiated to mature cells. We have first differentiated the iPS cells to endothelial cells. The expression of Dll4 gene, known to be associated with the angiogenic development, was increased and the branching in the tube formation was reduced in PAI-1 deficient iPS derived endothelial cells (PAI-1 iPS-ECs). Furthermore, PAI-1 iPS-ECs were detached from dish-bottom more easily than control iPS-ECs when the cells were cultured on gelatin-coated dishes. These results suggest that PAI-1 could play critical roles in differentiation and maturation of endothelial cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2015 2014 2013

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (10 results)

  • [Journal Article] Endogenously Generated Plasmin at the Vascular Wall Injury Site Amplifies Lysine Binding Site-Dependent Plasminogen Accumulation in Microthrombi.2015

    • Author(s)
      Brzoska T, Tanaka-Murakami A, Suzuki Y, Sano H, Kanayama N, Urano T.
    • Journal Title

      PLoSONE

      Volume: 10 Issue: 3 Pages: 1371-1371

    • DOI

      10.1371/journal.pone.0122196

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury.2014

    • Author(s)
      Kapitsinou P.P., Sano H., Michael M., Kobayashi H., Davidoff O., Bian A., Yao B., Zhang M.Z., Harris R.C., Duffy K.J., Erickson-Miller C.L., Sutton T.A., Haase V.H.
    • Journal Title

      J Clin Invest.

      Volume: 124 Issue: 6 Pages: 2396-2396

    • DOI

      10.1172/jci69073

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Binding of thrombin-activated platelets to a fibrin scaffold through αIIbβ3evokes phosphatidylserine exposure on their cell surface2013

    • Author(s)
      Brzoska T, Suzuki Y, Mogami H, Sano H, Urano T
    • Journal Title

      PLoS One

      Volume: 8(2) Issue: 2 Pages: 55466-55466

    • DOI

      10.1371/journal.pone.0055466

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] PAI-1欠損患者由来iPS細胞を用いた血管内皮細胞機能の解析2015

    • Author(s)
      佐野秀人、大津真、岩城孝行、長橋ことみ、Brzoska Tomasz 、鈴木優子、金山尚裕、浦野哲盟
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府市
    • Year and Date
      2015-05-21 – 2015-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genenration and differentiation of iPS cells derived from plasminogen activator inhibitor-1 deficient patient2015

    • Author(s)
      Sano H, Otsu M, Iwaki T, Nagahashi K, Brzoska T, Suzuki Y, Kanayama N, Urano T
    • Organizer
      第92回 日本生理学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-03-21 – 2015-03-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Genenration and differentiation of inducible pluripotent stem (iPS) cells derived from plasminogen activator inhibitor-1 deficient patient2014

    • Author(s)
      Sano H, Otsu M, Iwaki T, Nagahashi K, Suzuki Y, Kanayama N, Urano T
    • Organizer
      22nd International Congress on Fibrinolysis and Proteolysis
    • Place of Presentation
      フランス、マルセイユ
    • Year and Date
      2014-07-06 – 2014-07-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Plasminogen Activator Inhibitor-1欠損患者からのiPS細胞樹立2014

    • Author(s)
      佐野秀人、大津真、岩城孝行、長橋ことみ、鈴木優子、金山尚弘、浦野哲盟
    • Organizer
      第36回日本血栓止血学会学術集会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-05-29 – 2014-05-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] Generation of inducible pluripotent stem (iPS) cells from plasminogen activator inhibitor-1 deficient patient and differentiation into endothelial cells2014

    • Author(s)
      Sano H, Otsu M, Iwaki T, Nagahashi K, Suzuki Y, Kanayama N, Urano T
    • Organizer
      18th International Vascular Biology Meeting
    • Place of Presentation
      京都市
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Generation of inducible pluripotent stem (iPS) cells from plasminogen activator inhibitor-1 deficient patient and differentiation into endothelial cells2014

    • Author(s)
      Hideto Sano
    • Organizer
      The 18th International Vascular Biology Meeting
    • Place of Presentation
      Kyoto, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] Plasminogen Activator Inhibitor-1欠損患者からのiPS細胞樹立2014

    • Author(s)
      佐野秀人
    • Organizer
      第36回日本血栓止血学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] Genenration and differentiation of inducible pluripotent stem (iPS) cells derived from plasminogen activator inhibitor-1 deficient patient2014

    • Author(s)
      Hideto Sano
    • Organizer
      22nd International Congress on Fibrinolysis and Proteolysis
    • Place of Presentation
      Marseille, France
    • Related Report
      2013 Research-status Report
  • [Presentation] Generation of inducible pluripotent stem (iPS) cells from plasminogen activator inhibitor-1 deficient patient2013

    • Author(s)
      Hideto Sano
    • Organizer
      XIVth International Workshop Molecular & Cellular Biology of Plasminogen Activation
    • Place of Presentation
      University of Notre Dame, Indiana, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Generation of inducible pluripotent stem (iPS) cells from plasminogen activator inhibitor-1 deficient patient2013

    • Author(s)
      Sano H, Otsu M, Iwaki T, Nagahashi K, Suzuki Y, Kanayama N, Urano T
    • Organizer
      XIVth International Workshop on Molecular and Cellular Biology of Plasminogen Activation
    • Place of Presentation
      University of Notre Dame
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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