Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial.

Background: Preclinical studies have suggested that transurethral injections of autologous myoblasts can aid in regeneration of the rhabdosphincter, and fibroblasts in reconstruction of the urethral submucosa. We aimed to compare the effectiveness and tolerability of ultrasonography-guided injections of autologous cells with those of endoscopic injections of collagen for stress incontinence.

Methods: Between 2002 and 2004, we recruited 63 eligible women with urinary stress incontinence. 42 of these women were randomly assigned to receive transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts, and 21 to receive conventional endoscopic injections of collagen. The first primary outcome measure was an incontinence score (range 0-6) based on a 24-hour voiding diary, a 24-hour pad test, and a patient questionnaire. The other primary outcome measures were contractility of the rhabdosphincter and thickness of both the urethra and rhabdosphincter. Analysis was by intention to treat. This trial is registered with Controlled-Trials.com, number CCT-NAPN-16630.

Findings: At 12-months' follow-up, 38 of the 42 women injected with autologous cells were completely continent, compared with two of the 21 patients given conventional treatment with collagen. The median incontinence score decreased from a baseline of 6.0 (IQR 6.0-6.0; where 6 represents complete incontinence), to 0 (0-0) for patients treated with autologous cells, and 6.0 (3.5-6.0) for patients treated with collagen (p<0.0001). Ultrasonographic measurements showed that the mean thickness of the rhabdosphincter increased from a baseline of 2.13 mm (SD 0.39) for all patients to 3.38 mm (0.26) for patients treated with autologous cells and 2.32 mm (0.44) for patients treated with collagen (p<0.0001). Contractility of the rhabdosphincter increased from a baseline of 0.58 mm (SD 0.32) to 1.56 mm (0.28) for patients treated with autologous cells and 0.67 mm (0.51) for controls (p<0.0001). The change in the thickness of the urethra after treatment was not significantly different between treatment groups. No adverse effects were recorded in any of the 63 patients.

Interpretation: Long-term postoperative results and data from multicentre trials with larger numbers of patients are needed to assess whether injection of autologous cells into the rhabdosphincter and the urethra could become a standard treatment for urinary incontinence.