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Production of a structurally and functionally biomimetic 3D muscle tissue construct using cell sheet-based tissue engineering

Research Project

Project/Area Number 26702018
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionTokyo Women's Medical University

Principal Investigator

Takahashi Hironobu  東京女子医科大学, 医学部, 助教 (00710039)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords組織工学 / 再生医療 / 細胞シート / 骨格筋 / 筋組織 / 配向制御 / 神経細胞 / 血管内皮細胞
Outline of Final Research Achievements

In mature skeletal muscle, the muscle fibers are highly oriented to produce its mechanical functions, and vasculature and neurons also have well-organized structures. Using a patterned thermoresponsive culture substrate, we produced a cell sheet composed of aligned skeletal muscle myoblasts. This cell sheet was attached on a 3D gel and then incubated in differentiation medium. As a result, contractile muscle tissue construct was successfully produced. The muscle contraction was observed by electrical stimulation, and it was suppressed by the addition of some kinds of ion channel blockers. In addition, human neurons and human endothelial cells were incorporated within the multilayer cell sheets for creating a complex tissue construct. Both type of cells formed oriented networks guided by the myoblast orientation. The structural design and sequential functionalization in future work could lead to truly biomimetic tissue generation, and development of in-vitro physiological tissue models.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • Research Products

    (11 results)

All 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Cell sheet-based tissue engineering for organizing anisotropic tissue constructs produced using microfabricated thermoresponsive substrates2015

    • Author(s)
      Takahashi H and Okano T
    • Journal Title

      Advanced Healthcare Materials

      Volume: 4 Issue: 16 Pages: 2388-2407

    • DOI

      10.1002/adhm.201500194

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Anisotropic cellular network formation in engineered muscle tissue through the self-organization of neurons and endothelial cells2015

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masamichi Nakayama, Masayuki Yamato, Teruo Okano
    • Journal Title

      Advanced Healthcare Materials

      Volume: 4 Issue: 3 Pages: 356-360

    • DOI

      10.1002/adhm.201400297

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 細胞シート技術により作製した配向構造を有する骨格筋組織の機能評価2016

    • Author(s)
      高橋宏信、清水達也、中山正道、大和雅之、岡野光夫
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Micropatterned thermoresponsive materials for designing 3D microstructures in engineered tissue constructs2015

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      2015 MRS Fall Meeting & Exhibit
    • Place of Presentation
      ボストン(アメリカ)
    • Year and Date
      2015-11-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞シートとパターン化技術を用いた3D組織構築技術の現状と展望2015

    • Author(s)
      高橋宏信
    • Organizer
      第37回日本バイオマテリアル学会大会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2015-11-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 表面パターニング技術による細胞シートの配向制御と3次元組織への応用2015

    • Author(s)
      高橋宏信、清水達也、中山正道、大和雅之、岡野光夫
    • Organizer
      第64回高分子討論会
    • Place of Presentation
      東北大学(宮城県・仙台市)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Anisotropic network formation of neurons and endothelial cells in engineered muscle tissue construct2015

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masamichi Nakayama, Masayuki Yamato, Teruo Okano
    • Organizer
      The Society For Biomaterials 2015 Annual Meeting
    • Place of Presentation
      North Carolina(USA)
    • Year and Date
      2015-04-15 – 2015-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Anisotropic network formation of neurons and endothelial cells in engineered muscle tissue construct2015

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masamichi Nakayama, Masayuki Yamato, Teruo Okano
    • Organizer
      The Society For Biomaterials 2015 Annual Meeting
    • Place of Presentation
      シャーロット(アメリカ)
    • Year and Date
      2015-04-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 筋芽細胞の自己配向挙動を利用した異方性を有する三次元組織の構築2015

    • Author(s)
      高橋宏信、清水達也、中山正道、大和雅之、岡野光夫
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 配向制御型細胞シートを用いた異方性を有する筋組織の構造制御2014

    • Author(s)
      高橋宏信、清水達也、中山正道、大和雅之、岡野光夫
    • Organizer
      第36回日本バイオマテリアル学会大会
    • Place of Presentation
      タワーホール船堀(東京都・江戸川区)
    • Year and Date
      2014-11-17 – 2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] The use of anisotropic cell sheets for controlling cellular networks in engineered tissue constructs2014

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masamichi Nakayama, Masayuki Yamato, Teruo Okano
    • Organizer
      第63回高分子討論会
    • Place of Presentation
      長崎大学(長崎県・長崎市)
    • Year and Date
      2014-09-24 – 2014-09-26
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2017-05-10  

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