title: Recombinant insulin-like growth factor-1 activates satellite cells in the mouse urethral rhabdosphincter.
abstract: BACKGROUND
  The goal of this study is to demonstrate the efficacy of a new method for the treatment of urinary incontinence by stimulation of urethral rhabdosphincter satellite cells. We show that satellite cells do exist in the sphincter muscle of retired male mice breeders by staining for c-Met, a satellite cell specific protein. Once activated by recombinant mouse Insulin-like Growth Factor-1(rIgf-1), the satellite cells develop into muscle cells within the rhabdosphincter thereby potentially strengthening it.
  
  
  METHODS
  20 μl (1 μg/μl) of rIgf-1 was surgically injected directly into the urethral wall of retired male mouse breeders. Mice injected with phosphate buffered saline (PBS) were used as controls. 4 weeks later, urethras were harvested and serially-sectioned through the sphincter for routine hematoxylin-eosin staining as well as immunohistochemical staining with satellite cell specific anti-c-Met antibody and proliferation specific anti-Ki-67 antibody.
  
  
  RESULTS
  Anti-c-Met antibody positive cells (c-Met+) were identified in the rhabdosphincter. c-Met+ cells increased by 161.8% relative to controls four weeks after rIGF-1 injection. Anti- Ki-67 antibody positive cells were identified and characterized as cells with centrally located nuclei in striated muscle bundles of rIGF-1 treated animals.
  
  
  CONCLUSIONS
  Satellite cells in the mouse rhabdosphincter can be activated by rIGF-1 treatment, which subsequently are incorporated into existing skeletal muscle bundles. Using this approach, the rhabdosphincter can be induced to regenerate and potentially strengthen via satellite cell activation and likely improve urinary continence.
authors.affiliation: Department of Anatomy and Cell Biology, University of Pennsylvania, 240 S, 40th Street, Philadelphia, PA 19104, USA. wenjie@dental.upenn.edu.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wei
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Howard
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Macarak
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D014521:Urethra / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D014549:Urinary Incontinence / Q000188:drug therapy
chemical_list: D011994:Recombinant Proteins; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D019859:Proto-Oncogene Proteins c-met