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Development of 3D cultured skeletal muscle tissue for elucidation of molecular mechanisms of muscle aging

Research Project

Project/Area Number 19K11369
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KISHIDA TSUNAO  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (00370205)

Co-Investigator(Kenkyū-buntansha) 新井 祐志  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449)
清水 一憲  名古屋大学, 工学研究科, 准教授 (70402500)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨格筋細胞 / ダイレクトコンヴァージョン / サルコペニア / 3次元培養 / 再生医学 / 再生医療 / ダイレクト・コンヴァージョン / バイオマイクロシステム / 老化
Outline of Research at the Start

サルコペニアの病態を分子レベルで解析するためのツールとして、生理的な老化を反映する培養3Dヒト筋組織の開発が必要であるが、これには3つの要素技術が必要である。すなわち、①老化筋芽細胞、②3Dスキャフォールド、③機能評価系。最近我々は、ヒト筋芽細胞を線維芽細胞から誘導する独創的な技術を開発した。高齢者から得た線維芽細胞から誘導した筋芽細胞は老化しており、上記の①に有用な理想的な細胞である。さらに我々は、②、③も独自技術を開発している。本研究では、老化筋組織の解析に最適な培養3Dヒト筋組織を開発し、サルコペニアの分子メカニズムの解明に応用する基盤を確立する。

Outline of Final Research Achievements

The goal of this study is to establish a fundamental technology that contribute to the elucidation of the molecular mechanisms of sarcopenia. Myoblasts were seeded in a fibrin-based gel, and three-dimensional muscle tissue was formed by several days of differentiation culture using differentiation induction medium. Immunostaining revealed numerous myotubular cells that possess sarcomere structures. An electrical stimulation resulted in contraction of the 3D muscle tissue. The tension generated by the electro-stimulated muscle tissue was measured using a contraction force measurement microdevice, showing that the contraction force tended to increase during the culture period.

Academic Significance and Societal Importance of the Research Achievements

従来の方法よりも優れた骨格筋組織の培養方法を確立することに成功し、得られた骨格筋組織が高い機能を有することを確認できた。(Shimizu K,Kishida T, et al.J Biosci Bioeng. 2020 )。本研究で作成した骨格筋組織は、筋老化や筋肉の機能においての基礎研究のためのツールとしてのみならず、移植用の骨格筋組織を供給することも期待できるので、外傷や様々な骨格筋組織欠損に対する新しい有効な再生医療法に繋がることが期待される

Report

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

    (16 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (8 results) (of which Overseas: 8 results)

  • [Journal Article] ALK5 i II Accelerates Induction of Adipose-Derived Stem Cells toward Schwann Cells through a Non-Smad Signaling Pathway2021

    • Author(s)
      Seiji Sawai 1, Tsunao Kishida , Shin-Ichiro Kotani , Shinji Tsuchida , Ryo Oda , Hiroyoshi Fujiwara, Kenji Takahashi , Osam Mazda , Yoshihiro Sowa
    • Journal Title

      Stem Cells Int .

      Volume: Oct. 15 Pages: 1-11

    • DOI

      10.1155/2021/8307797

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treadmill running prevents atrophy differently in fast- versus slow-twitch muscles in a rat model of rheumatoid arthritis2021

    • Author(s)
      Yoichiro Kamada , Shogo Toyama , Yuji Arai , Hiroaki Inoue , Shuji Nakagawa , Yuta Fujii Kenta Kaihara , Tsunao Kishida , Osam Mazda , Kenji Takahashi
    • Journal Title

      J Muscle Res Cell Motil .

      Volume: Dec;42(3-4) Issue: 3-4 Pages: 429-441

    • DOI

      10.1007/s10974-021-09610-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteogenic Response to Polysaccharide Nanogel Sheets of Human Fibroblasts After Conversion Into Functional Osteoblasts by Direct Phenotypic Cell Reprogramming2021

    • Author(s)
      Nakai K, Yamamoto K, Kishida T, Kotani SI, Sato Y, Horiguchi S, Yamanobe H, Adachi T, Boschetto F, Marin E, Zhu W, Akiyoshi K, Yamamoto T, Kanamura N, Pezzotti G, Mazda O.
    • Journal Title

      Front Bioeng Biotechnol .

      Volume: Sep 3;9:713932 Pages: 713932-713932

    • DOI

      10.3389/fbioe.2021.713932

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanical stimulation of chondrocytes regulates HIF-1α under hypoxic conditions2021

    • Author(s)
      Shimomura S, Inoue H, Arai Y, Nakagawa S, Fujii Y, Kishida T, Shin-Ya M, Ichimaru S, Tsuchida S, Mazda O, Takahashi K.
    • Journal Title

      Tissue Cell .

      Volume: Aug;71:101574. Pages: 101574-101574

    • DOI

      10.1016/j.tice.2021.101574

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.2021

    • Author(s)
      Sowa Y, Kishida T, Louis F, Sawai S, Seki M, Numajiri T, Takahashi K, Mazda O
    • Journal Title

      Cells

      Volume: 10 Issue: 3 Pages: 65-76

    • DOI

      10.3390/cells10030605

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of contractile skeletal muscle tissues using directly converted myoblasts from human fibroblasts.2020

    • Author(s)
      Shimizu K, Ohsumi S, Kishida T, Mazda O, Honda H.
    • Journal Title

      J Biosci Bioeng.

      Volume: 129(5) Pages: 632-637

    • NAID

      120007164830

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ダイレクトコンヴァージョン誘導筋芽細胞を用いた3D組織の構築と機能評価2022

    • Author(s)
      岸田綱郎・松田 修
    • Organizer
      電子情報通信学会 OME研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ダイレクトリプログラミングで誘導した筋芽細胞を用いた三次元組織の構築と機能評価2019

    • Author(s)
      大隅早紀、清水一憲、岸田綱郎、松田修、本多裕之
    • Organizer
      再生医療学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 褐色脂肪細胞及びその調整方法2021

    • Inventor(s)
      岸田綱郎、松田修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 細胞の調整方法2021

    • Inventor(s)
      山本健太、岸田綱郎、素輪善弘、山本俊郎、松田 修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 尿路上皮細胞への誘導剤及び尿路上皮細胞の誘導方法2021

    • Inventor(s)
      井上裕太、浮村理、岸田綱郎 松田修
    • Industrial Property Rights Holder
      京都府公立大学法人、セルアクシア株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 骨芽細胞及びその調整方法2021

    • Inventor(s)
      山本健太、岸田綱郎、山本俊郎、松田 修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 骨芽細胞の調製方法及び骨芽細胞誘導剤2021

    • Inventor(s)
      山本健太、岸田綱郎、山本俊郎、松田 修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] シュワン細胞及びその調製方法2021

    • Inventor(s)
      素輪善弘、岸田綱郎、松田 修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 骨芽細胞及びその調製方法2021

    • Inventor(s)
      山本健太、岸田綱郎、山本俊郎、松田 修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 骨格筋細胞及びその調製方法2021

    • Inventor(s)
      若尾純子, 岸田綱郎, 田尻達郎, 松田 修
    • Industrial Property Rights Holder
      京都府公立大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Acquisition Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas

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Published: 2019-04-18   Modified: 2025-03-27  

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