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Establishment of immune torelance induction therapy for FVIII inhibitors by subcutaneous implantation of blood outgrowth endothelial cells

Research Project

Project/Area Number 24591559
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNara Medical University

Principal Investigator

MATSUI HIDETO  奈良県立医科大学, 医学部, 講師 (00571027)

Co-Investigator(Renkei-kenkyūsha) HOTTA Akitsu  京都大学, 助教 (50578002)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血友病 / インヒビター / 細胞移植 / 免疫寛容 / 制御性T細胞 / 免疫寛容導入 / 遺伝子・細胞治療 / 血友病A / 遺伝子治療 / 細胞治療 / 細胞療法
Outline of Final Research Achievements

The levels of FVIII inhibitors began to decline within 6 weeks after subcutaneous BOECs implantation and finally, the inhibitor levels had declined less than 5 BUs after the multiple implantations of transduced BOECs.The significant numbers of CD4+ CD25+ Foxp3 regulatory T cells were detected in spleen and draining lymph nodes of these partially tolerized mice and these suppressive effects against cFVIII could be adoptively transferred to naïve hemophilia recipient mice. We show that FVIII releasing subcutaneous depots play an important role of immunomodulatory effects that have a potential to reduce the levels of anti-FVIII inhibitor titers.

Report

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

    (18 results)

All 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Invited: 2 results) Book (4 results)

  • [Journal Article] Delivery of full-length factor VIII using a piggyBac transposon vector to correct a mouse model of hemophilia A2014

    • Author(s)
      Hideto Matsui, Naoko Fujimoto, Noriko Sasakawa, Yasuhide Ohinata, Midori Shima, Shinya Yamanaka, Mitsuhiko Sugimotom Akitsu Hotta
    • Journal Title

      PLOS ONE

      Volume: 9(8) Issue: 8 Pages: e104957-e104957

    • DOI

      10.1371/journal.pone.0104957

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A novel cell-sheet technology that achieves durable factor VIII delivery in a mouse model of hemophilia A2013

    • Author(s)
      Kohei Tatsumi, Mitsuhiko Sugimoto, David Lillicrap, Midori Shima, Kazuo Ohashi, Teruo Okano, Hideto Matsui
    • Journal Title

      PLOS ONE

      Volume: 8(12)

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endothelial progenitor cell-based therapy for hemophilia A2012

    • Author(s)
      Hideto Matsui
    • Journal Title

      International Journal of Hematology

      Volume: 95(2) Pages: 119-124

    • NAID

      10030267050

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 血友病の診療の進歩と今後の課題---血友病遺伝子・細胞治療の方向性2014

    • Author(s)
      松井英人
    • Organizer
      第56回日本小児血液・がん学会学術集会
    • Place of Presentation
      岡山市
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 血友病Aイヌモデルを用いた自己細胞移植による新規血友病A細胞治療法の開発検討2014

    • Author(s)
      野田正志、松井英人、松成泰典、越智すなお、嶋 緑倫、中山正成、杉本充彦
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2014-09-09 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 血友病Aに対する新規遺伝子・細胞治療戦略~自己細胞移植による細胞治療2014

    • Author(s)
      松井英人
    • 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
    • Invited
  • [Presentation] Successful long-term phenotypic correction of hemophilia A mice by multi-layered endothelial cell sheet transplantation2014

    • Author(s)
      Hideto Matsui, Masashi Noda, Rie Utoh, Kohei Tatsumi, Kazuo Ohashi, Midori Shima, Mitsuhiko Sugimoto, Teruo Okano
    • Organizer
      The ASGCT 17th Annual Meeting
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Long-term phenotypic correction of hemophilia a by non-viral piggyBac transposon vector2013

    • Author(s)
      Hideto Matsui, Mitsuhiko Sugimoto, Midori Shima, Naoko Fujimoto, Akitsu Hotta
    • Organizer
      The ASGCT 16th Annual Meeting
    • Place of Presentation
      Salt Lake City, U.S.A
    • Related Report
      2013 Research-status Report
  • [Presentation] Establishment of novel cell-based therapy for hemophilia A2013

    • Author(s)
      Hideto Matsui Mitsuhiko Sugimoto, Kohei Tatsumi, Kazuo Ohashi, Midori Shima, Teruo Okano
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Research-status Report
  • [Presentation] Successful long-term phenotypic correction of hemophilia A mice by engineering functional factor VIII delivery system in vivo using autologous endothelial cell sheets.2013

    • Author(s)
      Hideto Matsui, Kohei Tatsumi, Kazuo Ohashi, Midori Shima, Mitsuhiko Sugimoto, Teruo Okano
    • Organizer
      ASH 55th Annual Meeting
    • Place of Presentation
      New Orleans, U.S.A
    • Related Report
      2013 Research-status Report
  • [Presentation] 自己血管内皮前駆細胞移植による新規血友病A細胞療法の確立

    • Author(s)
      松井英人、辰巳公平、大橋一夫、杉本充彦、嶋緑倫、岡野光夫
    • Organizer
      第34回日本血栓止血学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] microRNA制御凝固第VIII因子発現レンチウイルスベクターによる新規血友病A遺伝子治療

    • Author(s)
      松井英人、杉本充彦、David Lillicrap、嶋緑倫
    • Organizer
      第19回肝細胞研究会
    • Place of Presentation
      札幌市
    • Related Report
      2012 Research-status Report
  • [Presentation] Establishment of the novel piggyBac transposon vector for the treatment of hemophilia A

    • Author(s)
      Hideto Matsui, Mitsuhiko Sugimoto, Midori Shima, Naoko Fujimoto, Akitsu Hotta
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都市
    • Related Report
      2012 Research-status Report
  • [Presentation] Anti-hemophilic properties of BAY 86-6150, a recombinant FVIIa variant, under blood flow

    • Author(s)
      Masaaki Doi, Mitsuhiko Sugimoto, Hideto Matsui, Yasunori Matsunari, Midori Shima, Jian-Ming Gu, Ji-Yun Kim, Volker Laux, John E Murphy, Timothy Myles
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都市
    • Related Report
      2012 Research-status Report
  • [Book] カラーテキスト 血液病学第2版 第3章 血液疾患の診断:主要兆候と検査値異常の解釈 E 血栓傾向の診察と鑑別2013

    • Author(s)
      松井英人、杉本充彦
    • Publisher
      中外医学社
    • Related Report
      2013 Research-status Report
  • [Book] カラーテキスト 血液病学第2版 第9章 出血・血栓性疾患 H 血栓症2013

    • Author(s)
      松井英人、杉本充彦
    • Publisher
      中外医学社
    • Related Report
      2013 Research-status Report
  • [Book] EBM 血液疾患の治療 2013-2014 V. 出血・血栓性疾患 9. 深部静脈血栓症に対する対策と治療2012

    • Author(s)
      松井英人、杉本充彦
    • Publisher
      中外医学社
    • Related Report
      2012 Research-status Report
  • [Book] 最新疾患モデルと病態解明、創薬応用研究、細胞医薬創製研究の最前線 最新疾患モデル動物,ヒト化マウス、モデル細胞、ES・iPS細胞を利用した病態解明から創薬まで 第2章 8 血液疾患 1) 血友病モデル犬を用いた創薬/臨床応用研究2012

    • Author(s)
      松井英人
    • Publisher
      メデイカルドウ
    • Related Report
      2012 Research-status Report

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

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