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Engineering of a matured muscle tissue construct by electrical stimulation-induced exercise and co-culturing iPS cell-derived neurons

Research Project

Project/Area Number 16H05909
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
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, 講師 (00710039)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2017: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2016: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords組織工学 / 再生医療 / メカノバイオロジー / 筋組織 / 神経組織
Outline of Final Research Achievements

Skeletal muscle physiology and the mechanisms of muscle diseases can be effectively studied by an in-vitro tissue model produced by tissue engineering. In this study, a human skeletal muscle tissue was produced by our newly developed method. To mimic native muscles, we focused on mechanical stresses. This study demonstrated that periodic exercise induced by continuous electrical stimulation enhanced the contractile ability of the engineered tissue. On the other hand, muscle contraction is controlled by nerve system in the body. From this viewpoint, we also attempted to produce a neuron-muscle tissue construct. Human iPS cells-derived motor neurons were seeded onto the tissue construct, and then the resultant tissue showed potential that human neurons physiologically connected to the engineered muscles. This new tissue engineering method could lead to truly biomimetic muscle tissue generation, and development of in-vitro physiological tissue models.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は骨格筋組織の成熟化を目指すことを通じて、筋の成長メカニズムを知り、それを制御することに繋げることができると期待される。この成果によって構築される組織は創薬研究における組織モデルとして有用である。生体に近い組織を構築できることは、その一部が欠損することで起こる様々な筋疾患に対する治療法の開発にも繋がる。本研究はその対象となる疾患を筋肉が原因の疾患のみならず、神経が関与する筋疾患にも拡大できることも示すことができた。さらに、老化に伴う筋萎縮のような問題は高齢者にとって幅広く関わりがあるため、筋萎縮を解決できる可能性を持つ本研究が高齢社会に与えるインパクトは特に大きいと考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results)

  • [Journal Article] Thermally-triggered fabrication of cell sheets for tissue engineering and regenerative medicine2019

    • Author(s)
      Hironobu Takahashi, Teruo Okano
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 138 Pages: 276-292

    • DOI

      10.1016/j.addr.2019.01.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineered Human Contractile Myofiber Sheets as a Platform for Studies of Skeletal Muscle Physiology2018

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Teruo Okano
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 13932-13932

    • DOI

      10.1038/s41598-018-32163-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 組織モデルとしての応用を目指した収縮能を有するヒト骨格筋組織の構築2019

    • Author(s)
      高橋宏信、清水達也、岡野光夫
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Functionalization of a human skeletal muscle tissue construct using a fibrin-based gel for tissue modeling2018

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      5th TERMIS World Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Engineering a functional muscle tissue using a fibrin-based gel for tissue modeling2018

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      29th Annual Conference of the European Society for Biomaterials 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] フィブリンゲルを用いたヒト骨格筋組織の機能化と継続的な収縮運動による成熟化2018

    • Author(s)
      高橋宏信、清水達也、大和雅之、岡野光夫
    • Organizer
      第40回日本バイオマテリアル学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 組織モデルとしての応用を目指した組織工学手法によるヒト骨格筋組織の構築2018

    • Author(s)
      高橋宏信、清水達也、大和雅之、岡野光夫
    • Organizer
      日本動物実験代替法学会第31回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 機能的な骨格筋組織の構築および継続的な収縮運動が収縮能に及ぼす影響2018

    • Author(s)
      高橋宏信、清水達也、大和雅之、岡野光夫
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞シート技術を利用した三次元組織の構造制御手法による生体模倣組織の構築2017

    • Author(s)
      高橋宏信
    • Organizer
      第36回日本動物細胞工学会シンポジウム
    • Place of Presentation
      キャンパスイノベーションセンター(東京都・港区)
    • Year and Date
      2017-03-29
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 筋芽細胞の自己配向制御能を利用した骨格筋組織の構築と収縮機能の評価2017

    • Author(s)
      高橋宏信、清水達也、大和雅之、岡野光夫
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
  • [Presentation] Production of contractile muscle tissue constructs based on cell sheet tissue engineering2017

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      The Society For Biomaterials 2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] Micro-fabricated thermoresponsive polymer-grafted surface for producing contractile muscle tissue construct2017

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      2017 MRS Spring Meeting & Exhibit
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cell sheet-based tissue engineering for producing a contractile muscle tissue construct2017

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      28th Annual Conference of the European Society for Biomaterials 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] フィブリンゲルを用いた骨格筋組織の構築と組織モデルとしての応用2017

    • Author(s)
      高橋宏信、清水達也、大和雅之、岡野光夫
    • Organizer
      第39回日本バイオマテリアル学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 組織構築における配向構造制御のためのバイオインターフェースの設計2017

    • Author(s)
      高橋宏信、清水達也、大和雅之、岡野光夫
    • Organizer
      第27回日本MRS年次大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 3次元組織の配向制御技術の開発と生体模倣組織構築への応用2016

    • Author(s)
      高橋宏信
    • Organizer
      日本バイオマテリアル学会シンポジウム2016
    • Place of Presentation
      福岡国際会議場(福岡県・福岡市)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 高分子パターニング技術および細胞シート操作技術による3次元組織の構造制御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65回高分子討論会
    • Place of Presentation
      神奈川大学(神奈川県・横浜市)
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] Production of a contractile muscle tissue construct based on cell sheet technology2016

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masayuki Yamato, Teruo Okano
    • Organizer
      TERMIS-AP meeting 2016
    • Place of Presentation
      Tamsui (Taiwan)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cell sheet-based tissue engineering for organizing anisotropic muscle tissue constructs produced using microfabricated thermoresponsive materials2016

    • Author(s)
      Hironobu Takahashi, Tatsuya Shimizu, Masamichi Nakayama, Masayuki Yamato, Teruo Okano
    • Organizer
      10th World Biomaterials Congress
    • Place of Presentation
      Montreal (Canada)
    • Year and Date
      2016-05-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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