In animal models, autologous myoblasts and fibroblasts have been used to reconstruct the urethral complex: myoblasts to regenerate the rhabdosphincter and fibroblasts to treat the atrophy of the mucosa. This method might, therefore, be suitable for the treatment of stress urinary incontinence (SUI) in women.OBJECTIVE
To assess the safety and efficacy of autologous myoblast and fibroblast injection for the treatment of female SUI.DESIGN AND INTERVENTION
This study, conducted during 2004-2005, included women with urodynamically confirmed SUI whose symptoms had not improved with pelvic floor exercises. Exclusion criteria were urge urinary incontinence or marked hypermobility of the urethra. A muscle biopsy (biceps) was taken from each patient, and was used to isolate myoblasts and fibroblasts. The cells were grown separately for 6-8 weeks. The myoblasts were then suspended in serum, and the fibroblasts were suspended in serum mixed with collagen. Using a transurethral ultrasonography (TRUS)-guided injection device, the myoblast suspension was injected into the rhabdosphincter at two different levels, and the fibroblast-collagen suspension was injected circumferentially into the submucosa at three levels. Urethroscopy was performed at the end of the operation. Patients were instructed to perform regular rhabdosphincter training and use transvaginal electrical stimulation for 4 weeks after treatment. The outcome measures were analyzed before, and 1 year after treatment.OUTCOME MEASURES
The primary outcome measures were the incontinence score (comprising a 24 h voiding diary, a 24 h pad test and a patient questionnaire), contractility of the rhabdosphincter, and thickness of the rhabdosphincter and urethra (as measured by TRUS). Secondary outcome measures were the incontinence quality-of-life score, patterns of individual muscle activity (as measured by kinesiological electromyography at rest and during voluntary contraction), urodynamic tests, and adverse effects.RESULTS
In total, 123 women were included, of whom 119 had 1-year follow-up data. The mean patient age was 62.8 years. One year after treatment, 94 (79%) patients were continent, 16 (13%) patients had substantially improved symptoms, and 9 (8%) patients had slightly improved symptoms. Significant improvements were observed in the incontinence score (P=0.001) and the incontinence quality-of-life score (P=0.001). The mean rhabdosphincter contractility score improved from 0.65 to 1.39 (P=0.001), mean rhabdosphincter thickness improved from 2.1 to 3.4 mm (P = 0.001), and mean individual muscle activity improved from 34.0 to 15.0 μV at rest (P = 0.001)and from 43.1 to 55.4 μV during voluntary contraction (P=0.001). Urinary maximum flow rate significantly increased but only slightly (P=0.001), and postvoid residual urine volume decreased (P=0.001). There were no complications during the procedure, and no postsurgery adverse events were reported. Twelve patients required catheter placement after the procedure, for a maximum of 2 days.CONCLUSIONS
TRUS-guided injection of myoblasts and fibroblasts into the rhabdosphincter and submucosa, respectively, is a safe and effective method for treating female SUI. Long-term results will be required to confirm these findings.