Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

INTRODUCTION AND HYPOTHESIS: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.

Adult stem cell sources for skeletal and smooth muscle tissue engineering.

INTRODUCTION: Tissue engineering is an innovative field with enormous developments in recent years. These advances are not only in the understanding of how stem cells can be isolated, cultured and manipulated but also in their potential for clinical applications. Thus, tissue engineering when applied to skeletal and smooth muscle cells is an area that bears high benefit for patients with muscular diseases or damage. Most of the recent research has been focused on use of adult stem cells. These cells have the ability to rejuvenate and repair damaged tissues and can be derived from different organs and tissue sources. Recently there are several different types of adult stem cells, which have the potential to function as a cell source for tissue engineering of skeletal and smooth muscles. However, to build neo-tissues there are several challenges which have to be addressed, such as the selection of the most suitable stem cell type, isolation techniques, gaining control over its differentiation and proliferation process. CONCLUSION: The usage of adult stem cells for muscle engineering applications is promising. Here, we summarize the status of research on the use of adult stem cells for cell transplantation in experimental animals and humans. In particular, the application of skeletal and smooth muscle engineering in pre-clinical and clinical trials will be discussed.