Induction of transplantable myogenic cells from pluripotent stem cells

• Project/Area Number: 24590497
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: SUZUKI Yuko 独立行政法人国立精神・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): TAKEDA Shin'ichi 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, 部長 (90171644)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 幹細胞 / 再生医療 / iPS細胞 / ジストロフィン / 筋ジストロフィー / 骨格筋 / 移植 / 人工多能性幹細胞 / 再生医学

Outline of Final Research Achievements

Induced pluripotent stem cells are a promising tool for regenerative medicine of muscular dystrophies. Here, we compared the cell surface antigens on human myoblasts and human fibroblasts, and found that CD56 and CD271 specifically recognize human myoblasts. Next, we tested whether EZ-sphere method is effective to induce transplantable muscle stem/progenitor cells by transplantation into immunodeficient mdx mice (DMD model mice) and found that iPS-derived muscle stem/progenitor cells participate in muscle regeneration.

Research Products

• [Journal Article] Possibility of small-molecule-based pharmacotherapy for sarcopenia (2015)
  • Author(s): Watanabe Y, Miyagoe-Suzuki Y
  • Journal Title: The Journal of Physical Fitness and Sports Medicine Volume: 4 Issue: 1 Pages: 73-82
  • DOI: 10.7600/jpfsm.4.73
  • NAID: 130005130595
  • ISSN: 2186-8123, 2186-8131
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Doublecortin marks a new population of transiently amplifying muscle progenitor cells and is required for myofiber maturation during skeletal muscle regeneration (2015)
  • Author(s): Ogawa R, Ma Y, Yamaguchi M, Ito T, Watanabe Y, Ohtani T, Murakami S, Uchida S, De Gaspari P, Uezumi A, Nakamura M, Miyagoe-Suzuki Y, Tsujikawa K, Hashimoto N, Braun T, Tanaka T, Takeda S, Yamamoto H, Fukada S
  • Journal Title: Development Volume: 142 Issue: 1 Pages: 51-61
  • DOI: 10.1242/dev.112557
  • Peer Reviewed / Open Access
• [Journal Article] Low intensity training of mdx mice reduces carbonylation and increases expression levels of proteins involved in energy metabolism and muscle contraction. (2015)
  • Author(s): Hyzewicz J, Tanihata J, Kuraoka M, Ito N, Miyagoe-Suzuki Y, Takeda S
  • Journal Title: Free Radic Biol Med Volume: 82 Pages: 122-136
  • DOI: 10.1016/j.freeradbiomed.2015.01.023
  • Peer Reviewed / Open Access
• [Journal Article] G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy (2015)
  • Author(s): Hayashiji N, Yuasa S, Miyagoe-Suzuki Y, Hara M, Ito N, Hashimoto H, Kusumoto D, Seki T, Tohyama S, Kodaira M, Kunitomi A, Kashimura S, Takei M, Saito Y, Okata S, Egashira T, Endo J, Sasaoka T, Takeda S, Fukuda K
  • Journal Title: Nature Communications Volume: 6 Issue: 1 Pages: 6745-6745
  • DOI: 10.1038/ncomms7745
  • Peer Reviewed / Open Access
• [Journal Article] Imatinib attenuates dystrophic condition in severe mouse dystrophy and inhibits both proliferation and fibrosis-marker expression in muscle mesenchymal progenitors (2013)
  • Author(s): Ito T, Ogawa R, Uezumi A, Watanabe Y, Ohtani T, Miyagoe-Suzuki Y, Tsujikawa K, Takeda S, Yamamoto H, Fukada S
  • Journal Title: Neuromuscular Disorders. Volume: 23 Issue: 4 Pages: 349-56
  • DOI: 10.1016/j.nmd.2012.10.025
  • Peer Reviewed
• [Journal Article] Impaired viability of muscle precursor cells in muscular dystrophy with glycosylation defects and amelioration. of its severe phenotype by limited gene expression. (2013)
  • Author(s): Kanagawa M, et. al.
  • Journal Title: Hum Mol Genet Volume: 22 Issue: 15 Pages: 3003-3015
  • DOI: 10.1093/hmg/ddt157
  • Peer Reviewed
• [Journal Article] Capsaicin mimics mechanical load-induced intracellular signaling events: involvement of TRPV1-mediated calcium signaling in induction of skeletal muscle hypertrophy. (2013)
  • Author(s): Ito N, Ruegg UT, Kudo A, Miyagoe-Suzuki Y, Takeda S.
  • Journal Title: Channels Volume: 7 Issue: 3 Pages: 221-224
  • DOI: 10.4161/chan.24583
  • Peer Reviewed
• [Journal Article] Activation of calcium signaling through Trpvl by nNOS and peroxynitrite as a key trigger of skeletal muscle hypertrophy. (2013)
  • Author(s): Ito N, et al
  • Journal Title: Nature medicine Volume: 19 Issue: 1 Pages: 101-106
  • DOI: 10.1038/nm.3019
  • Peer Reviewed
• [Journal Article] Laminin regulates postnatal oligodendrocyte production by promoting oligodendrocyte progenitor survival in the subventricular zone. (2012)
  • Author(s): Relucio J, Menezes MJ, Miyagoe-Suzuki Y, Takeda S, Colognato H.
  • Journal Title: Glia Volume: 60 Issue: 10 Pages: 1451-1467
  • DOI: 10.1002/glia.22365
  • Peer Reviewed
• [Journal Article] Calcitonin receptor and Odz4 are differently expressed in Pax7-positive cells during skeletal muscle regeneration (2012)
  • Author(s): Yamaguchi M, Ogawa R, Watanabe Y, Uezumi A, Miyagoe-Suzuki Y, Tsujikawa K, Yamamoto H, Takeda S, Fukada S
  • Journal Title: J. Mol. Histol. Volume: 43 Issue: 5 Pages: 581-7
  • DOI: 10.1007/s10735-012-9421-3
  • Peer Reviewed
• [Presentation] 難治性筋疾患に対する細胞移植治療法の開発 (2015)
  • Author(s): 鈴木 友子
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 横浜パシフィコ、神奈川県
  • Year and Date: 2015-03-20
• [Presentation] Sphere法を用いたヒトiPS細胞からの骨格筋系譜幹細胞の誘導 (2015)
  • Author(s): 鈴木良次、成田麻子、鈴木正寿、鈴木友子、武田伸一
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 横浜パシフィコ、神奈川県
  • Year and Date: 2015-03-20
• [Presentation] Derivation of transplantable myogenic cells from human induced pluripotent stem cells (iPS) cells using a sphere-based culture method. (2015)
  • Author(s): Narita A, Suzuki R, Suzuki M, Miyagoe-Suzuki Y, Takeda S
  • Organizer: The 18th Takeda Science Foundation Symposium on Bioscience
  • Place of Presentation: 武田薬品研修所、吹田市、大阪府
  • Year and Date: 2015-01-15 – 2015-01-17
• [Presentation] Sphere法を用いたヒトiPS細胞からの骨格筋幹・前駆細胞の分化誘導． (2014)
  • Author(s): 成田麻子，鈴木良次，鈴木正寿，鈴木友子，武田伸一
  • Organizer: 第9回筋ジストロフィー治療研究合同発表会
  • Place of Presentation: 吉池旅館、箱根、神奈川県
  • Year and Date: 2014-11-01
• [Presentation] Induction of skeletal muscle from induced pluripotent stem (iPS) cells by sphere-based culture (2014)
  • Author(s): Narita A, Suzuki R, Miyagoe-Suzuki Y, Takeda S
  • Organizer: FASEB research conference-Skeletal Muscle Satellite and Stem Cells
  • Place of Presentation: Ｓｔｅａｍｂｏａｔ Ｇｒａｎｄ, Ｓｔｅａｍｂｏａｔ Ｓｐｒｉｎｇｓ， Colorado, USA
  • Year and Date: 2014-07-25
• [Presentation] 筋ジストロフィーとiPS細胞―筋ジストロフィーの再生医療の実現化を目指して (2012)
  • Author(s): 鈴木 友子
  • Organizer: 第54回 日本小児神経学会総会
  • Place of Presentation: ロイトン札幌
  • Invited
• [Book] Translational research in muscular dystrophy (2015)
  • Author(s): Stem cell-based cell therapy for Duchenne muscular dystrophy
  • Total Pages: 15
  • Publisher: Ｓｐｒｉｎｇｅｒ
• [Book] Muscular Dystrophy (2012)
  • Author(s): Miyagoe-Suzuki Y, Ono Y, Fukada S and Takeda S.
  • Total Pages: 15
  • Publisher: INTECH