title: Intraurethral transfer of satellite cells by myofiber implants results in the formation of innervated myotubes exerting tonic contractions.
abstract: OBJECTIVE
  We investigated a new method of muscle precursor cell transfer in the urethra for the treatment of urinary incontinence, consisting of implanting myofibers with their satellite cells.
  
  
  METHODS
  In preliminary experiments to test the regenerative capacities of satellite cells histological analysis was performed on days 7 and 30 after the implantation of myofiber cores in the urethra of 6 female pigs. In the main experiments 11 pigs underwent baseline urodynamics, followed by endoscopic destruction of the striated urethral sphincter located around the distal urethra (day 0). On day 30 circular myofiber strips in 7 experimental cases and adipocytes in 4 controls were implanted in the proximal urethra. Seven days later (day 37) 1 case was sacrificed to verify satellite cell activation. On day 60 urodynamics were performed without and with curarization. Urethral cryosections were immunostained for desmin (activated satellite cells), fast myosin heavy chain/bungarotoxin (myotubes/acetylcholine receptors), neurofilament/vesicular acetylcholine transporter (nerve endings) and CD45/CD68 (inflammatory response).
  
  
  RESULTS
  Preliminary histological studies revealed a myogenic process consisting of myofiber degeneration and satellite cell activation (day 7), followed by myotube formation replacing parental myofibers (day 30). In the main experiments endoscopic injury abolished striated urethral sphincter activity. Implantation of myofiber strips generated a pressure peak that decreased after curarization (mean+/-SEM 71.5+/-17.8 vs 33.5+/-14.8 cm H2O, p=0.031) and reappeared 60 minutes later, revealing that this action was tonic and under neural control. Nerve endings connected to the acetylcholine receptors of myotubes were observed on day 60. An inflammatory response was observed only on day 7 in the myofiber implantation group. Adipocyte implantation resulted in no significant intraurethral pressure changes.
  
  
  CONCLUSIONS
  Urethral implantation of myofibers regenerates as myotubes that exert tonic activity under neural control. This has potential clinical value as a means to create an additional striated urethral sphincter.
authors.affiliation: Service d'Urologie, Centre de Recherches Chirurgicales, Centre Hospitalier Universitaire Henri Mondor, France.
authors.forename: Constant
authors.initials: C
authors.lastname: Lecoeur
authors.forename: Salem
authors.initials: S
authors.lastname: Swieb
authors.forename: Laurent
authors.initials: L
authors.lastname: Zini
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rivière
authors.forename: Hélène
authors.initials: H
authors.lastname: Combrisson
authors.forename: Romain
authors.initials: R
authors.lastname: Ghérardi
authors.forename: Claude
authors.initials: C
authors.lastname: Abbou
authors.forename: René
authors.initials: R
authors.lastname: Yiou
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D009119:Muscle Contraction; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology*; D032446:Myoblasts / Q000637:transplantation*; D013552:Swine; D014521:Urethra / Q000502:physiology*; D014550:Urinary Incontinence, Stress / Q000503:physiopathology / Q000601:surgery; D014563:Urodynamics