Generation of human skeletal muscle in the muscles of immunodeficient mice

• Project/Area Number: 15K12675
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Sports science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology (2016); Fujita Health University (2015)
• Principal Investigator: Uezumi Akiyoshi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 専門副部長 (60434594)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 筋衛星細胞 / 細胞表面マーカー / ヒト細胞 / 移植 / 骨格筋幹細胞

Outline of Final Research Achievements

Skeletal muscle contains stem cell population called satellite cells. Satellite cells can generate myotube in vitro but there is a critical difference between myotube and skeletal muscle tissue. In addition, use of human cells is needed for the medical research. It is possible that making human muscle fibers in vivo by transplanting human satellite cells into the muscles of immunodeficient mice. However, it is difficult to achieve efficient transplantation of human satellite cells because purification method of human satellite cells has not been established. In this study, we discovered novel marker of human satellite cells, CD82. We demonstrated that efficient transplantation of human satellite cells into immunodeficient mice can be done by utilizing CD82 as a positive selection marker. We believe that our results provide useful information for the study of human skeletal muscle cells.

Research Products

• [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
  • Peer Reviewed / Open Access
• [Journal Article] Identification, Isolation, and Characterization of Mesenchymal Progenitors in Mouse and Human Skeletal Muscle (2016)
  • Author(s): Akiyoshi Uezumi, Takehiro Kasai, and Kunihiro Tsuchida
  • Journal Title: Methods in Molecular Biology Volume: 1460 Pages: 241-253
  • DOI: 10.1007/978-1-4939-3810-0_17
  • ISBN: 9781493938087, 9781493938100
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche (2015)
  • Author(s): Yamaguchi M, Watanabe Y, Ohtani T, Uezumi A, Mikami N, Nakamura M, Sato T, Ikawa M, Hoshino M, Tsuchida K, Miyagoe-Suzuki Y, Tsujikawa K, Takeda S, Yamamoto H, Fukada S
  • Journal Title: Cell Rep Volume: 13(2) Issue: 2 Pages: 302-314
  • DOI: 10.1016/j.celrep.2015.08.083
  • NAID: 120006957413
  • Peer Reviewed / Open Access
• [Journal Article] Evidence of Notch-Hesr-Nrf2 Axis in Muscle Stem Cells, but Absence of Nrf2 Has No Effect on Their Quiescent and Undifferentiated Stat (2015)
  • Author(s): Yamaguchi M, Murakami S, Yoneda T, Nakamura M, Zhang L, Uezumi A, Fukuda S, Kokubo H, Tsujikawa K, Fukada S
  • Journal Title: PLoS One Volume: 10(9) Issue: 9 Pages: 138517-138531
  • DOI: 10.1371/journal.pone.0138517
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pro-IGF-II ameliorates age-related inefficient regenerative response by orchestrating self-reinforcement mechanism of muscle regeneration. (2015)
  • Author(s): Ikemoto-Uezumi M, Uezumi A, Tsuchida K, Fukada S, Yamamoto H, Yamamoto N, Shiomi K, Hashimoto N.
  • Journal Title: Stem Cells Volume: in press Issue: 8 Pages: 2456-2468
  • DOI: 10.1002/stem.2045
  • Peer Reviewed
• [Presentation] ヒト骨格筋由来前駆細胞の新規マーカー探索とその応用 (2016)
  • Author(s): 上住 聡芳
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-19
• [Presentation] 高品質なヒト骨格筋由来幹・前駆細胞の獲得とその応用 (2016)
  • Author(s): 上住聡芳
  • Organizer: 第３６回日本眼薬理学会
  • Place of Presentation: 帝京大学（東京都・板橋区）
  • Invited
• [Presentation] 筋間質の間葉系前駆細胞による骨格筋組織の維持 (2016)
  • Author(s): 上住聡芳
  • Organizer: 第２回日本筋学会学術集会
  • Place of Presentation: NCNP（東京都・小平市）
  • Invited
• [Presentation] Roles of interstitial mesenchymal progenitors in skeletal muscle homeostasis (2016)
  • Author(s): Uezumi A
  • Organizer: Symposium at Stem Cell Institute in University of Minnesota Medical School“Cardiac and Skeletal Muscle Stem Cell and Regeneration”
  • Place of Presentation: University of Minnesota Medical School, MN, USA
  • Int'l Joint Research / Invited
• [Presentation] Maintenance of skeletal muscle by interstitial mesenchymal progenitors (2016)
  • Author(s): Uezumi A
  • Organizer: FASEB SRC
  • Place of Presentation: Keystone Resort Conference Center, CO, USA
  • Int'l Joint Research
• [Presentation] 骨格筋内在性間葉系前駆細胞を標的としたサルコペニアの予防法開発 (2015)
  • Author(s): 上住 聡芳
  • Organizer: 第１回日本筋学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-08-08
  • Invited