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Development of iPS cell-derived platelet preparation with bone fusion promoting effect

Research Project

Project/Area Number 19K09615
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionChiba University

Principal Investigator

Shiga Yasuhiro  千葉大学, 大学院医学研究院, 特任准教授 (90568669)

Co-Investigator(Kenkyū-buntansha) 高山 直也  千葉大学, 大学院医学研究院, 准教授 (10584229)
大鳥 精司  千葉大学, 大学院医学研究院, 教授 (40361430)
折田 純久  千葉大学, 大学院医学研究院, 特任准教授 (60638310)
稲毛 一秀  千葉大学, 大学院医学研究院, 助教 (80793629)
曽根 正光  北海道大学, 低温科学研究所, 助教 (90599771)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsiPS細胞由来血小板 / 骨癒合促進 / サイトカイン / 骨癒合 / 骨形成促進 / iPS細胞由来人工巨核球・血小板凍結乾燥製剤 / 多血小板血漿 / 再生医療
Outline of Research at the Start

ヒト白血球抗原(HLA)を欠損させたユニバーサルタイプのiPS由来人工血小板を大量生産し,血小板による骨修復の根源的メカニズムに基づくユニバーサルタイプの高機能人工血小板を開発し,安全性の高い画期的な骨癒合技術を開発すること,およびその安全性および有効性を確認する.

Outline of Final Research Achievements

In recent years, the clinical use of platelet-rich plasma has been expanding, but the non-uniformity of quality and effect has become a problem because it is derived from autologous blood. In this study, we promoted the development of a function-enhanced artificial platelet preparation that replaces autologous PRP by utilizing the production base of iPS cell-derived artificial platelets, which is an allogeneic platelet transfusion product. As a result, we proved the bone fusion effect of freeze-dried iPS platelet preparation in rat spinal surgery, and published the paper for the first time in the world. Furthermore, we succeeded in creating a function-enhanced megakaryocyte strain by improving the forced expression system of a specific cytokine having a tissue repair effect.

Academic Significance and Societal Importance of the Research Achievements

本研究では血小板を大量に製造可能な巨核球細胞株が遺伝子操作可能であり高機能血小板を作出できることを証明した.これは遺伝子治療を組み込んだ再生医療の細胞治療モデルを世界で初めて示すことに繋がる.自己血由来PRPと異なり,パッケージされた凍結乾燥製剤で骨折や手術における早期骨癒合が効率的に促進されれば,患者のADL・QOL向上に大きく寄与するものと考えられる.その他にもこれまで治療が困難であった潰瘍性難治創や神経損傷・脊髄損傷等に対しても有用である可能性が期待される.

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (9 results)

All 2021 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] The Effect of Megakaryocytes and Platelets Derived from Human-Induced Pluripotent Stem Cells on Bone Formation2021

    • Author(s)
      Masashi Sato, Yasuhiro Shiga, Naoya Takayama, Masamitsu Sone, Kentaro Kosaka, Itsuro Motegi, Norichika Mizuki, Kazuhide Inage, Yawara Eguchi, Miyako Narita, Sumihisa Orita, Koji Eto, Seiji Ohtori
    • Journal Title

      Spine Surgery and Related Research

      Volume: 5 Issue: 3 Pages: 196-204

    • DOI

      10.22603/ssrr.2020-0226

    • NAID

      130008044530

    • ISSN
      2432-261X
    • Year and Date
      2021-05-27
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The Platelet derived from induced pluripotent stem cells accelerates bone union with adequate rigidity in posterolateral lumbar fusion surgery model in rats2021

    • Author(s)
      Yasuhiro Shiga, Masashi Sato, Norichika Mizuki, Sumihisa Orita, Kazuhide Inage, Yawara Eguchi, Miyako Narita, Takashi Hozumi, Geundong Kim, Takuma Odagiri, Tomohito Mukaihata, Satoshi Maki, Takeo Furuya, Kentaro Kosaka, Naoya Takayama, Koji Eto, Seiji Ohtori
    • Organizer
      ISSLS Anual meeting2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞由来巨核球・血小板製剤の骨癒合促進効果2021

    • Author(s)
      志賀康浩,佐藤雅,水木誉凡,折田純久,稲毛一秀,江口和,穂積崇史,金勤東,江藤浩之, 高山直也,小坂 健太朗,大鳥 精司
    • Organizer
      第94回 日本整形外科学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] iPS細胞由来血小板製剤は骨癒合促進効果を有する 自己血由来多血小板血漿を凌駕する組織修復効果の可能性2021

    • Author(s)
      志賀康浩,佐藤雅,水木誉凡,折田純久,稲毛一秀,江口和,金勤東,穂積崇史,小田切拓磨,向畑智仁,牧聡,古矢丈雄,小坂健太朗,高山直也,江藤浩之,大鳥精司
    • Organizer
      第50回日本脊椎脊髄病学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The Platelet derived from induced pluripotent stem cells accelerates bone union with adequate rigidity in posterolateral lumbar fusion surgery model in rats2021

    • Author(s)
      志賀康浩
    • Organizer
      国際腰椎学会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] iPS細胞由来巨核球・血小板製剤の骨癒合促進効果2021

    • Author(s)
      志賀康浩
    • Organizer
      日本整形外科学会 学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] iPS細胞由来血小板製剤の骨癒合促進効果2021

    • Author(s)
      志賀康浩
    • Organizer
      日本自己血輸血学会 学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] iPS細胞由来血小板製剤は骨癒合促進効果を有する ー自己血由来多血小板血漿を凌駕する組織修復効果の可能性ー2021

    • Author(s)
      志賀康浩
    • Organizer
      日本脊椎脊髄病学会 学術集会
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 巨核球および 血小板を含む 凍結乾燥製剤2019

    • Inventor(s)
      江藤浩之 大鳥精司 志賀康浩
    • Industrial Property Rights Holder
      江藤浩之 大鳥精司 志賀康浩
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-224781
    • Filing Date
      2019
    • Related Report
      2020 Research-status Report
    • Overseas

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Published: 2019-04-18   Modified: 2023-01-30  

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