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Development of bone adhesive treatment with functionally modified platelets

Research Project

Project/Area Number 19K22675
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionChiba University

Principal Investigator

Eto Koji  千葉大学, 大学院医学研究院, 教授 (50286986)

Co-Investigator(Kenkyū-buntansha) 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)
志賀 康浩  千葉大学, 大学院医学研究院, 特任准教授 (90568669)
曽根 正光  千葉大学, 大学院医学研究院, 特任助教 (90599771)
Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords人工血小板 / iPS細胞 / 骨癒合 / 骨折治療 / 血小板 / HLA
Outline of Research at the Start

難治性の複雑骨折などでは、早期のADL・QOL回復のため、迅速な骨癒合の実現が臨床上の大きな課題となっている。申請者のグループは血小板を多く含む血漿成分を患部へ局所注入することで骨融合促進が可能なことを動物モデルで確認した。一方、申請者らは、iPS細胞技術を用いてヒト白血球抗原(HLA)を欠損させ,自己免疫反応の誘発を抑制したユニバーサルタイプの人工血小板を大量に生産する手法を確立した。そこで本研究では、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機能拡張型人工血小板を作製し、動物モデルなどを用いて、安全性の高い画期的な骨癒合技術を開発することを目指す。

Outline of Final Research Achievements

Platelet Rich Plasma (PRP) administration treatment is known to accelerate repairment of bone fracture by bone adhesion machinery. However, stable supply of autologous PRP, along with the diversity of individual PRP quality, never allow the given action in real clinical setting. Our research program confirmed that iPSC-derived megakaryocytes and platelets, whereby we already established mass production methods and stability, contain several growth factors for bone adhesion, resulting in significantly improved bone adhesion in a rat lumbar bone graft model, compared to that by PRP. Moreover, we transduced lentiviral vectors harboring multiple growth factors for tissue repair by iPSC-derived megakaryocytes, which also successfully produced functionally modified platelets.

Academic Significance and Societal Importance of the Research Achievements

脊椎固定術は、難治性複雑骨折や腰椎変性疾患に対して行われ、早期のADL(日常生活動作)回復に寄与するための迅速な骨癒合の実現が必須である。iPS細胞由来血小板製剤の大量製造技術を応用し、均一性の担保された大量生産可能な血小板製剤の骨癒合への応用が確認されたことから、高齢者や外傷患者などのPRPの安定調達が困難な症例に有効と期待できる。さらに遺伝子改変した巨核球細胞株をいわば生産工場、人工血小板をキャリアとして生理活性物質を患部に輸送するための新たなドラッグデリバリーシステムが確立できた。

Report

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

    (6 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Book (1 results)

  • [Journal Article] Development of platelet replacement therapy using human induced pluripotent stem cells2021

    • Author(s)
      Nakamura Sou、Sugimoto Naoshi、Eto Koji
    • Journal Title

      Development, Growth & Differentiation

      Volume: 63 Issue: 2 Pages: 178-186

    • DOI

      10.1111/dgd.12711

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation and manipulation of human iPSC-derived platelets2021

    • Author(s)
      Sugimoto Naoshi、Eto Koji
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 78 Issue: 7 Pages: 3385-3401

    • DOI

      10.1007/s00018-020-03749-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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: _

    • NAID

      130008044530

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] iPSC-Derived Platelets Depleted of HLA Class I Are Inert to Anti-HLA Class I and Natural Killer Cell Immunity.2020

    • Author(s)
      Suzuki D, Flahou C, Yoshikawa N, Stirblyte I, Hayashi Y, Sawaguchi A, Akasaka M, Nakamura S, Higashi N, Xu H, Matsumoto T, Fujio K, Manz MG, Hotta A, Takizawa H, Eto K, Sugimoto N.
    • Journal Title

      Stem Cell Reports.

      Volume: 14 Issue: 1 Pages: 49-59

    • DOI

      10.1016/j.stemcr.2019.11.011

    • NAID

      120006777032

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SHARPIN at the nexus of integrin, immune, and inflammatory signaling in human platelets.2019

    • Author(s)
      Kasirer-Friede A, Tjahjono W, Eto K, Shattil SJ.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 116 Issue: 11 Pages: 4983-4988

    • DOI

      10.1073/pnas.1819156116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Book] 新規の創薬モダリティ 細胞医薬2020

    • Author(s)
      河本 宏、辻 真博
    • Total Pages
      243
    • Publisher
      羊土社
    • ISBN
      9784758103909
    • Related Report
      2020 Annual Research Report

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Published: 2019-07-04   Modified: 2022-01-27  

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