Hypothesis: 
To confirm long-term functional integration of expanded muscle precursor cells (MPCs) into the impaired external urethral sphincter (EUS) delivering clinically meaningful and persistent improvement of female stress urinary incontinence (SUI).  

Aims:
The aim of this clinical trial was to investigate the long-term efficacy and safety of transurethral ultrasound-guided injections of tissue-engineered autologous MPCs in resorbable collagen solution (MPCCOL) into the EUS to treat SUI in female patients.

Study Design
A blinded, prospective and randomised clinical trial included 30 female patients, randomised to receive either dose level one (80-100x106 cells) or two (120-150x106 cells) of autologous MPCCOL and a follow up of 6 months. After completion of this trial all patients were given the option to enrol into a long-term follow-up study, where key assessments of the main trial are repeated at 12, 24, 36, 48 and 60 months post injection. 

Methods:
MPCs were obtained by a skeletal muscle biopsy of the lower leg. After isolation, expansion and harvesting of MPCs in a certified GMP facility, the final product MPCCOL was implanted through transurethral ultrasound-guided injection into the EUS. The longitudinal study assessed safety and efficacy parameters at 12 months compared to baseline as follows: standardized 24h and 1h pad tests; reduction of incontinence episode frequency (IEF) by 3-day bladder diary using a mixed effects negative binomial regression model; validated continence questionnaires (ICIQ-UI-SF and ICIQ-LUTSqol). The study was approved by an appropriately constituted competent ethics committee.

Of the 30 patient who received treatment, 16 were assigned to dose level one and 14 to dose level two. Median age was 45 years and median BMI 22.9 kg/m2. The treatment overall (both groups) resulted in clinically meaningful and statistically significant reductions of 60.0% in IEF (rate ratio 0.40, 90% CI: 0.27 to 0.59, p<0.0001) at 6 months compared to baseline. Patients in the dose level two group had a greater improvement of 71.3% (rate ratio 0.29, 90% CI: 0.13 to 0.63, p=0.0044). 24h pad test weights demonstrated an overall reduction of 66% (23.61g, 90% CI: -30.9g to -16.3g, p<0.0001) overall and a reduction of 76.7% (24.0g, 90% CI: -34.9g to -13.3g, p=0.0003) in the dose level two group. Further, the treatment led to an improvement in quality of life (ICIQ questionnaires). No necrosis or signs of aberrant tissue formation were found in the pelvic MRI. Finally, no treatment-related serious adverse events were observed.
In the long-term follow-up study 13 patients completed the 12 months post-treatment assessment at the timepoint of the interim analysis. For the 12 patients which responded to the treatment at the 6 months period, the positive results were confirmed. Compared to baseline IEF demonstrated a reduction of 79.1% (rate ratio 0.21, 90% CI: 0.09 to 0.51, p=0.002) and 24h pad weights an overall reduction of 85.4% (20.30g, 90% CI: -26.13g to -14.47g, p<0.0001) remaining stable or improved compared to the 6-months period. At 12-months the safety profile remained sustained.

This is the first report on long-term 12 months results of tissue-engineered MPCCOL implantation in female SUI. The interim clinical data set, including the 12 months results from 12/30 patients, demonstrates the sustained efficacy and safety of MPCCOL. The improving clinical response until 6 months after treatment reflects the gradual functional recovery of muscular function over time and remains mostly unchanged at 12 months (interim long-term data). This is in line with the hypothesis of functional repair by neo-muscle formation by MPCs. The outpatient procedure proved to be feasible, safe and well-tolerated.

In conclusion, the findings support the hypothesis that sustained long-term functional repair is achieved through EUS regeneration by MPCCOL implantation in female SUI patients.

Continence 19S (2026) 102490
DOI: 10.1016/j.cont.2026.102490