title: Periurethral skeletal myofibre implantation in patients with urinary incontinence and intrinsic sphincter deficiency: a phase I clinical trial.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Cell therapy using muscle precursor cell (MPC) injections has shown promise for urinary incontinence due to intrinsic sphincter deficiency (ISD), but the cell-preparation process is complex and costly. Implantation of freshly isolated myofibres carrying MPCs, mainly satellite cells, was very efficient in repairing muscle damage in recent animal experiments. In a phase I clinical trial, we investigated whether periurethral myofibre implantation generated local myogenesis and improved continence in 10 patients (five men and five women) with ISD. We found that myofibre implantation increased intraurethral pressure and periurethral electromyographic activity in patients with ISD. There were no serious side-effects.
  
  
  OBJECTIVE
  To assess the safety of periurethral myofibre implantation in patients with urinary incontinence due to intrinsic sphincter deficiency (ISD) To assess the resulting myogenic process and effects on urinary continence.
  
  
  METHODS
  An open-label non-randomised phase I clinical trial was conducted in five men and five women with ISD (mean age, 62.5 years). A free muscle strip from the patient's gracilis muscle was implanted around the urethra as a means to deliver locally myofibres and muscle precursor cells (MPCs). Patients were assessed for collection formation and incomplete bladder emptying. The maximum urethral closure pressure (MUCP) and concomitant periurethral electromyographic (EMG) activity were recorded before surgery and 1 and 3 months after surgery. Continence was assessed using the 24-h pad test and self-completed questionnaires, for 12 months.
  
  
  RESULTS
  There were no serious side-effects. Continence improved significantly during the 12-month follow-up in four of the five women, including two who recovered normal continence. In the women, MUCP increased two-fold and de novo EMG periurethral activity was recorded. In the men, MUCP and EMG recordings showed similar improvements but the effect on continence was moderate. The few patients enrolled could affect these results.
  
  
  CONCLUSIONS
  This is the first report of a one-step procedure for transferring autologous MPCs via myofibre implantation in patients with ISD. EMG and urodynamic assessments showed improvement of periurethral muscle activity. Further work is needed to confirm and improve the therapeutic efficiency of this procedure.
authors.affiliation: Service d’Urologie, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre deTassigny, Créteil, France. rene.yiou@hmn.aphp.fr
authors.forename: René
authors.initials: R
authors.lastname: Yiou
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.forename: Catherine-Marie
authors.initials: CM
authors.lastname: Loche
authors.forename: François-Jerome
authors.initials: FJ
authors.lastname: Authier
authors.forename: Philippe
authors.initials: P
authors.lastname: Lecorvoisier
authors.forename: Pauline
authors.initials: P
authors.lastname: Jouany
authors.forename: Françoise
authors.initials: F
authors.lastname: Roudot-Thoraval
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Lefaucheur
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000637:transplantation*; D009130:Muscle, Smooth / Q000637:transplantation*; D017060:Patient Satisfaction; D020127:Recovery of Function; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014521:Urethra / Q000503:physiopathology*; D014549:Urinary Incontinence / Q000503:physiopathology / Q000601:surgery*; D014563:Urodynamics; D013520:Urologic Surgical Procedures / Q000379:methods*