RECONSTRUCTIVE UROLOGY

Autologous Myoblasts and Fibroblasts versus Collagen for Treatment of Stress Urinary Incontinence in Women: A Randomised Controlled Trial
Strasser H, Marksteiner R, Margreiter E, Pinggera GM, Mitterberger M, Frauscher F, Ulmer H, Fussenegger M, Kofler K, Bartsch G
Department of Urology, University of Innsbruck, Austria
Lancet. 2007 Jun 30;369(9580):2179-86

• 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.
  
  
• Editorial Comment
  In recent years, the knowledge and awareness for female stress urinary incontinence has grown with the result that a wide range of different treatment options has become available. Treatment options improved with the increased knowledge of pelvic floor dysfunction and surgical options became less invasive by the year.
  Obtaining autologous myoblasts of skeletal muscle-biopsies, cultivating them and transplanting them after differentiation into the external urethral sphincter herald a new era of incontinence therapy. In the current study of Strasser et al., 42 patients were treated by a transurethral, ultrasound-guided injection of myoblasts and fibroblasts. The control group of 21 patients received collagen in the conventional method.
  After a mean follow-up of 12 months, urinary continence and improvement of the urethral rhabdosphincter was evaluated with questionnaires, voiding diaries, pad tests, transurethral ultrasonograpy and electromyography. Out of those treated with autologous myoblasts and fibroblasts, over 90% were completely dry, whereas in the control group, a success rate of only 9% was recorded.
  Currently, experience with this new incontinence treatment comes from a single center, which has started to collaborate with others in order to verify the presented striking results. In addition to some doubts about the allocation concealment and ascertainment bias, it might be important which way the “material” is injected. The ultrasound-guided application might be more precise and effective than the classic visual-judged injections. The number of deposits needed to ensure good filling as well as coaptation of the urethral wall and thus compression of the urethral lumen, which must still be proven.
  The presented results, the development of the clinical pathways of this procedure and new sources of stem cells to be transplanted might be one of the most important achievements in reconstructive urology of the last decade. By presenting a minimal invasive technique with a precise application into the location for a physiological function, a treatment option to regenerate sphincter function and to prevent urinary incontinence at an early stage becomes feasible.
  Additional stem cell sources (1), which can be harvested easier and may be even true omnipotent stem cells in order to better reconstruct a rhabdosphincter are currently tested experimentally and might offer the possibility to treat high grade stress urinary incontinence.

Reference
1. Renninger M: Isolation of human spermatogonial cells from testicular parenchyma and differentiation towards different tissues of the three human germ layers. J Urol, 2007; 177: 56 (Abst #166).

Dr. Karl-Dietrich Sievert &
Dr. Arnulf Stenzl
Department of Urology
Eberhard-Karls-University Tuebingen
Tuebingen, Germany
E-mail: Arnulf.Stenzl@med.uni-tuebingen.de