Stem cell applications in regenerative medicine for stress urinary incontinence: A review of effectiveness based on clinical trials

Abstract

ABSTRACT Objective To evaluate the current state, therapeutic benefit and safety of urethral injection of autologous stem cells for the treatment stress urinary incontinence (SUI). Materials and methods A selective database search of PubMed, the Excerpta Medica dataBASE (EMBASE), Cochrane Library and Google Scholar was conducted to validate the effectiveness of stem cell-based therapy. The search included clinical trials published up until 4 January 2020, written in English, and included cohorts of women and men who had received stem cell-based therapy for SUI. The search used the following keywords in various combinations: ‘stem cell therapy’, ‘cell-based therapy for SUI’, ‘regenerative medicine for SUI’, and ‘tissue engineering’. The success rates were assessed according to cough test, urodynamics, pad tests, and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The primary endpoint was continence rate to measure objectively the effect of the treatment. Results We identified four clinical trials using local injections of adipose-derived stem cells (ADSCs), 11 trails with muscle-derived stem cells (MDSCs), and two trails with human umbilical cord blood stem cells (HUCBs) and total nucleated cells (TNCs). The median improvement rate of intrinsic sphincter deficiency after ADSCs, MDSCs, TNCs, HUCBs injections were 88%, 77%, 89%, 36% (improvement rate: 1–2 pads) at a mean (range) follow-up of 6 (1–72) months. The cell sources, methods of cell processing, cell number, and implantation techniques differed considerably between studies. Most of the periurethral injections were at the 3, 5, 7, and 9 o’clock positions and for submucosa were at the 4, 6, and 8 o’clock positions. No significant postoperative complications were reported. Conclusion Despite many challenges in stem cell-based therapy for treating SUI, it appears to provide, in both male and female patients, acceptable functional results with minimal side-effects and complications. In the future, more clinical trials should be funded in order to optimise stem cell-based therapy and evaluate long-term outcomes. Abbreviations ADSC: adipose-derived stem cell; BMSCs: bone marrow-derived mesenchymal stem cell; CLPP: cough leak-point pressure; FPL: functional profile length; HUCB: human umbilical cord blood stem cell; ICIQ-(QOL)(SF)(UI): International Consultation on Incontinence Questionnaire (Quality of life) (-Urinary incontinence Short Form) (-Urinary Incontinence); IIQ-7: Incontinence Impact Questionnaire-short form; I-QOL: Incontinence quality of life questionnaire; ISD: intrinsic urinary sphincter deficiency; MDSC: muscle-derived stem cell; MUCP: maximum urethral closure pressure; NR: not reported; Pdet-max: maximum detrusor pressure; PVR: post-void residual urine volume; Qmax: maximum urinary flow; QOL: quality of life; RP: radical prostatectomy; TNC: total nucleated cell; (S)UI: (stress) urinary incontinence; UDSCs: urine-derived stem cells; UTUS: upper tract ultrasonography; VLPP: Valsalva leak-point pressure