title: Transplantation of myocyte precursors derived from embryonic stem cells transfected with IGFII gene in a mouse model of muscle injury.
abstract: BACKGROUND
  Reconstruction of skeletal muscle tissue is hampered by the lack of availability of functional substitution of the tissue.
  
  
  METHODS
  Embryonic stem (ES) cells were transfected with the insulin-like growth factor (IGF) II gene and were selected with G418. The resultant cell clones were analyzed regarding their myogenic differentiation in vitro and in vivo.
  
  
  RESULTS
  The cells expressed early and late myogenic differentiation markers, including myoD, myogenin, and dystrophin in vitro. They had phosphorylated Akt within the cells, suggesting their activation by the secreted IGFII. Transplantation of the cells to injured anterior tibial muscle of mice significantly improved their motor functions compared to injured mice transplanted with undifferentiated ES cells and injured mice given vehicle alone. The transfected cells adapted to the injured muscle, formed myofibers positive for dystrophin and negative for MyoD and myogenin. Trichrome staining and toluidine blue staining support myofiber formation in vivo. The enzymatic activity of acetylcholine esterase suggested the functional activity of the regenerated motor units. The evoked electromyogram of anterior tibial muscle transplanted with the transfected cells showed significantly higher potentials compared to that transplanted with undifferentiated ES cells and that injected with phosphate-buffered saline (control injury). Electron microscopic examination confirmed the myofiber formation in the cells in vivo.
  
  
  CONCLUSIONS
  Transfection of IGFII gene into ES cells may be applicable for transplantation therapy of muscle damage due to injury and myopathies.
authors.affiliation: Departments of Immunology and Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kamochi
authors.forename: Manae S
authors.initials: MS
authors.lastname: Kurokawa
authors.forename: Hideshi
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Chieko
authors.initials: C
authors.lastname: Masuda
authors.forename: Erika
authors.initials: E
authors.lastname: Takada
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Manabu
authors.initials: M
authors.lastname: Sakakibara
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Natuki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Moroe
authors.initials: M
authors.lastname: Beppu
authors.forename: Haruhito
authors.initials: H
authors.lastname: Aoki
authors.forename: Noboru
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000166:cytology*; D015316:Genetic Therapy; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology*; D018482:Muscle, Skeletal / Q000293:injuries*; D012038:Regeneration; D033581:Stem Cell Transplantation; D014162:Transfection
chemical_list: D007335:Insulin-Like Growth Factor II