Generation of myogenic stem cells from iPS cells via blastocyst complementation.

• Project/Area Number: 16H07001
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Hiroshima University
• Principal Investigator: Ito Hikaru 広島大学, 医歯薬保健学研究科(医), 助教 (50587392)
• Research Collaborator: Asakura Atsushi University of Minnesota, Department of Neurology, Stem Cell Institute, Associate Professor ; Asakura Yoko University of Minnesota, Department of Neurology, Stem Cell Institute, Technical staff(Researcher2)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 再生医療 / 骨格筋幹細胞 / 胚盤胞胚補完法 / 発生工学 / 筋ジストロフィー / サルコペニア / 骨格筋 / キメラ / 再生医学 / 老化 / 移植・再生医療 / 発生・分化 / 動物 / 細胞・組織

Outline of Final Research Achievements

One attractive therapy is myogenic stem cell transplantation to provide dystrophin in Duchenne Muscular Dystrophy (DMD) patients. Recent work has reported the induced pluripotent stem cell (iPSC)-derived myogenic stem cell transplantation for therapeutic strategy for DMD. However, there is a limitation in this strategy, especially in low differentiation efficiency and poor reproducibility of iPSCs-derived myogenic stem cells. Therefore, in a blastocyst complementation method, the regeneration of an organ can be achieved by utilizing the defect in an organ which can be complemented by injecting patient-derived iPSCs into a non-human blastocyst.
In this study, we injected GFP (+) mouse iPSCs into skeletal muscle-less mouse blastocysts. iPSC-derived cells highly contributed to limb muscle of chimera. We also performed intramuscular injection of myogenic stem cells isolated from chimeric mice into mdx mice, and detected GFP (+) muscle fibers which also expressed donor-derived dystrophin.

Research Products

• [Int'l Joint Research] ミネソタ大学(米国)
• [Int'l Joint Research] ミネソタ大学 幹細胞研究所/ミネソタ大学 muscular dystrophy center(米国)
• [Journal Article] Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice (2018)
  • Author(s): Yamawaki Y, Yoshioka N, Nozaki K, Ito H, Oda K, Harada K, Shirawachi S, Asano S, Aizawa H, Yamawaki S, Kanematsu T, Akagi H
  • Journal Title: Brain research Volume: 1;1680 Pages: 13-38
  • DOI: 10.1016/j.brainres.2017.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Developmental YAPdeltaC determines adult pathology in a model of spinocerebellar ataxia type 1. (2017)
  • Author(s): Fujita K, Mao Y, Uchida S, Chen X, Shiwaku H, Tamura T, Ito H, Watase K, Homma H, Tagawa K, Sudol M, Okazawa H.
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 1864-1864
  • DOI: 10.1038/s41467-017-01790-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Generation of myogenic stem cells from iPS cells via blastocyst complementation. (2017)
  • Author(s): Hikaru Ito, Yoko Asakura, Atsushi Asakura
  • Organizer: 2017年度生命科学系学会合同年次大会（日本分子生物学会）
• [Presentation] Blastocyst complementation法を用いた骨格筋幹細胞の産生 (2017)
  • Author(s): 伊藤日加瑠、朝倉よう子、朝倉淳
  • Organizer: 第160回日本獣医学会学術集会
• [Presentation] Blastocyst complementation法を用いた骨格筋幹細胞の産生 (2017)
  • Author(s): 伊藤日加瑠, 朝倉よう子, 朝倉淳
  • Organizer: 日本解剖学会第72回中国・四国支部学術集会