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application of induced mesenchymal stem cells from human iPS cells to cell therapy in muscular dystrophy

Research Project

Project/Area Number 16K08725
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Suzuki Yuko  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 室長 (00342931)

Co-Investigator(Kenkyū-buntansha) 武田 伸一  国立研究開発法人国立精神・神経医療研究センター, その他部局等, 部長 (90171644)
Research Collaborator Takemura Fusako  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords間葉系幹細胞 / 筋ジストロフィー / 再生 / 移植治療 / 筋前駆細胞 / 骨格筋 / 分化 / ヒトiPS細胞 / 移植 / 筋再生 / 細胞移植 / 多能性幹細胞 / 骨格筋前駆細胞 / 人工多能性幹細胞 / 再生医療
Outline of Final Research Achievements

Mesenchymal stem cells (MSCs) may improve the efficiency of transplantation of myogenic cells into dystrophic muscle, because they have anti-inflammatory and immunomodulatory properties, protect cells from apoptosis, and secrete factors which support muscle growth. We induced MSCs (iMSC) from hiPSCs. FACS revealed that iMSC express MSC markers, CD73, CD90 and CD105. iMSC could be induced to differentiate into osteogenic, chondrogenic, and adipogenic cells.iMSCs showed higher proliferative potential than human bone marrow-derived MSCs (BM-MSC). Both MSCs promoted the differentiation of human myoblasts, when co-cultured by using the transwell, suggesting that MSCs secrete soluble factors which promote muscle differentiation. Unexpectedly, co-transplantation of iMSC with hiPSC-derived myogenic cells into immuno-deficient DMD model mice did not produce dystrophin-positive myofibers. The factors which inhibit differentiation of hiPSC-derived myogenic cells in vivo remain to be clarified.

Academic Significance and Societal Importance of the Research Achievements

筋ジストロフィーにおいては骨格筋線維が変性・壊死し、それを再生する組織幹細胞である筋衛星細胞の機能も病気の進行に伴い低下してくる。その一因として、骨格筋の間葉系前駆細胞の機能の低下があると言われている。我々はヒトiPS細胞から誘導した間葉系前駆細胞がヒト多能性幹細胞(iPS細胞)から誘導した筋前駆細胞の筋分化をin vitroにおいて促進することを明らかにした。今後は共移植に用いることで、その治療用細胞としての有用性と安全性を示すとともに、骨格筋の恒常性維持及び筋ジストロフィーの分子病態における間葉系前駆細胞の機能も明らかにしていく予定である。

Report

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

    (18 results)

All 2019 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 4 results) Book (2 results)

  • [Journal Article] Premyogenic progenitors derived from human pluripotent stem cells expand in floating culture and differentiate into transplantable myogenic progenitors2018

    • Author(s)
      Sakai-Takemura F, Narita A, Masuda S, Wakamatsu T, Watanabe N, Nishiyama T, Nogami K, Blanc M, Takeda S, Miyagoe-Suzuki Y
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 6555-6555

    • DOI

      10.1038/s41598-018-24959-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 筋ジストロフィー:神経・筋幹細胞による研究2018

    • Author(s)
      鈴木友子、武田伸一
    • Journal Title

      CLINICAL NEUROSCIENCE

      Volume: 36 Pages: 351-355

    • Related Report
      2017 Research-status Report
  • [Journal Article] Skeletal muscle generated from induced pluripotent stem cells- induction and application2017

    • Author(s)
      Miyagoe-Suzuki Y, Takeda S
    • Journal Title

      World J Stem Cells

      Volume: 9 Pages: 89-97

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Skeletal Muscle Cells Generated from Pluripotent Stem Cells2017

    • Author(s)
      Miyagoe-Suzuki Yuko、Asakura Atsushi、Suzuki Masatoshi
    • Journal Title

      Stem Cells International

      Volume: 2017 Pages: 1-2

    • DOI

      10.1155/2017/7824614

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 難治性筋疾患に対する細胞移植治療法の開発2017

    • Author(s)
      竹村英子、鈴木友子、武田伸一
    • Journal Title

      化学工業

      Volume: 68 Pages: 19-23

    • Related Report
      2017 Research-status Report
  • [Journal Article] Induction of pluripotent stem cells from a manifesting carrier of Duchenne muscular dystrophy and characterization of their X-inactivation status2017

    • Author(s)
      Yuko Miyagoe-Suzuki, Takashi Nishiyama, Miho Nakamura, Asako Narita, Fusako Takemura, Satoru Masuda, Narihiro Minami, Kumiko Murayama, Hirofumi Komaki, Yu ichi Goto, Shin’ichi Takeda
    • Journal Title

      Stem Cells International

      Volume: 2017 Pages: 1-9

    • DOI

      10.1155/2017/7906843

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cell-surface protein profiling identifies distinctive markers of progenitor cells in human skeletal muscle.2016

    • Author(s)
      Uezumi A, Nakatani M, Ikemoto-Uezumi M, Yamamoto N, Morita M, Yamaguchi A, Yamada H, Kasai T, Masuda S, Narita A, Miyagoe-Suzuki Y, Takeda S, Fukada S, Nishino I, Tsuchida K.
    • Journal Title

      Stem Cell Reports.

      Volume: 7 Issue: 2 Pages: 263-278

    • DOI

      10.1016/j.stemcr.2016.07.004

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト骨格筋前駆細胞の増殖と分化の制御機構の解析2019

    • Author(s)
      鈴木友子
    • Organizer
      第18回日本再生医療学会総会 シンポジウム36
    • Related Report
      2018 Annual Research Report
  • [Presentation] Stable induction of myogenic progenitors from human iPS cells using modified EZ sphere method2018

    • Author(s)
      Yuko Miyagoe-Suzuki, Fusako Sakai-Takemura, Ken’ichiro Nogami, Matthias Blanc, Ahmed Elhussieny, Shin’ichi Takeda
    • Organizer
      FASEB Science Research Conferences:"Skeletal muscle Satellite Cells and Regeneration
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多能性幹細胞を用いた難治性筋疾患に対する細胞移植治療法の開発2018

    • Author(s)
      鈴木友子
    • Organizer
      日本再生医療学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞からSphere法によって誘導される骨格筋前駆細胞の骨格筋再生能に関する解析2017

    • Author(s)
      鈴木 友子、増田 智、成田 麻子、竹村 英子、武田 伸一
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Robust derivation of transplantable skeletal muscle progenitor cells from human induced pluripotent stem (iPS) cells using a stirring bioreactor2017

    • Author(s)
      鈴木友子、増田 智、成田麻子、竹村英子、鈴木正寿、武田伸一
    • Organizer
      International Society for Stem Cell Research Annual meeting (ISSCR2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 沿軸中胚葉誘導を行うことでEZ sphere法によるヒトiPS細胞からの骨格筋分化誘導が安定化する2017

    • Author(s)
      竹村英子、増田 智、渡辺喜晴、成田麻子、鈴木友子、武田伸一
    • Organizer
      日本筋学会第3回学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞由来骨格筋系譜細胞はTGF-beta阻害により筋分化が促進する2017

    • Author(s)
      竹村英子、増田 智、渡辺喜晴、成田麻子、鈴木正寿、武田伸一、鈴木友子
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Characterization of skeletal myogenic cells derived from human iPS cells2016

    • Author(s)
      Narita A, Masuda S, Wakamatsu T, Suzuki M, Fukada S, Uezumi A, Takeda S, Miyagoe-Suzuki Y
    • Organizer
      International Society for Stem Cell Research Annual meeting
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2016-06-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Derivation of myogenic cells from human induced pluripotent stem (iPS) cells using a stirred bioreactor2016

    • Author(s)
      Miyagoe-Suzuki Y, Narita A, Masuda S, Takemura F, Nishiyama T, Ito N, Takeda S
    • Organizer
      Molecular Mechanisms Modulating Skeletal Muscle, Development and Homeostasis in Health and Disease Society for Muscle Biology Frontiers in Myogenesis
    • Place of Presentation
      アメリカ
    • Year and Date
      2016-06-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] Muscle Cell and Tissue-Current Status of Reseach Field, IntechOpen, London, 117-132, 20182018

    • Author(s)
      Nogami K, Blanc M, Takemura F, Takeda S, Miyagoe-Suzuki Y
    • Total Pages
      16
    • Publisher
      Intech
    • ISBN
      9781789840063
    • Related Report
      2018 Annual Research Report
  • [Book] Translational research in muscular dystrophy, eBOOK, 武田伸一、鈴木友子、森-吉村まどか編2016

    • Author(s)
      Yuko Miyagoe-Suzuki & Shin'ichi Takeda
    • Total Pages
      13
    • Publisher
      SPRINGER Japan
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-12-27  

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