title: Intramuscular transplantation of muscle-derived stem cells accelerates skeletal muscle healing after contusion injury via enhancement of angiogenesis.
abstract: BACKGROUND
  Muscle contusions are common muscle injuries. Although these injuries are capable of healing, incomplete functional recovery often occurs. Muscle-derived stem cells (MDSCs) are likely derived from blood vessel cells and have a multilineage differentiation potential.
  
  
  OBJECTIVE
  The aims of this study are (1) to find optimal timing of MDSC transplantation to enhance muscle healing by stimulating muscle regeneration and preventing scar tissue (fibrosis) formation after skeletal muscle contusion injury, and (2) to investigate the role of angiogenesis in the muscle-healing process after MDSC transplantation.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Muscle-derived stem cells were injected directly into injured tibialis anterior muscles of mice at various time points (1, 4, and 7 days) after the muscle contusion injury. Muscle regeneration, angiogenesis, and fibrosis formation were evaluated by histology and real-time polymerase chain reaction analysis, and functional recovery was measured by physiologic testing.
  
  
  RESULTS
  Transplantation of MDSCs at 4 days after injury significantly promoted angiogenesis, which was induced by high levels of vascular endothelial growth factor expression at week 1, and significantly increased muscle regeneration and muscle strength by week 2, when compared with the other groups. A decrease in fibrosis formation was observed at week 4, when compared with the other groups, after the transplantation of MDSCs at 4 and 7 days after injury.
  
  
  CONCLUSIONS
  Intramuscular injection of MDSCs at 4 days after injury improved and accelerated skeletal muscle healing by increasing angiogenesis and decreasing scar tissue formation.
  
  
  CONCLUSIONS
  These findings could contribute to the development of biologic treatments to aid in muscle healing after muscle injury.
authors.affiliation: Stem Cell Research Center, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Ota
authors.forename: Kenji
authors.initials: K
authors.lastname: Uehara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Terada
authors.forename: Kimimasa
authors.initials: K
authors.lastname: Tobita
authors.forename: Freddie H
authors.initials: FH
authors.lastname: Fu
authors.forename: Johnny
authors.initials: J
authors.lastname: Huard
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000473:pathology; D003288:Contusions / Q000473:pathology / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000502:physiology; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D018919:Neovascularization, Physiologic; D012038:Regeneration / Q000502:physiology; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse