Two phase I/II clinical trials for the treatment of urinary incontinence with autologous mesenchymal stem cells

Abstract

We proposed to evaluate the safety and feasibility of adipose-derived mesenchymal stem cells to treat endoscopically urinary incontinence after radical prostatectomy in men or female stress urinary. We designed two prospective, nonrandomized phase I-IIa clinical trials of urinary incontinence involving 9 men (8 treated) and 10 women to test the feasibility and safety of autologous mesenchymal stem cells for this use. Cells were obtained from liposuction containing 150 to 200 g of fat performed on every patient. After 4 to 6 weeks and under sedation, endoscopic intraurethral injection of the cells was performed. On each visit (baseline, 1, 3, 6, and 12 months), clinical parameters were measured, and blood samples, urine culture, and uroflowmetry were performed. Every patient underwent an urethrocystoscopy and urodynamic studies on the first and last visit. Data from pad test, quality-of-life and incontinence questionnaires, and pads used per day were collected at every visit. Statistical analysis is made by Wilcoxon signed-rank test. No adverse effects have been collected. Three men (37.5%) and five women (50%) showed an objective improvement of >50% (P < .05) and a subjective improvement of 70% to 80% from baseline. In conclusion, intraurethral application of stem cells derived from adipose tissue is a safe and feasible procedure to treat urinary incontinence after radical prostatectomy or in female stress urinary incontinence. A statistically significant difference was obtained for pad-test improvement in 3/8 men and 5/10 women. Our results encourage studies to confirm safety and to analyze efficacy. K E Y W O R D S adipose-derived stem cells, cellular therapy, male/female urinary incontinence, phase IIa clinical trial 1 | INTRODUCTION The International Continence Society defines urinary incontinence as "any involuntary loss of urine that is a social or hygienic problem." Following benign prostatic hyperplasia surgery, a mean of 0.5% to 2%

Stem Cells in Clinical Trials for Pelvic Floor Disorders: a Systematic Literature Review

“…Overall, 11 studies met the inclusion criteria and were incorporated into the final assessment [16][17][18][19][20][21][22][23][24][25][26]. Specifically, we found 7 papers dealing with stem cell therapy for stress urinary incontinence [16][17][18][19][20][21][22] and 4 with anal incontinence [23][24][25][26]. No papers concerning the use of SC for prolapse repair were retrieved.…”

“…To evaluate the impact of stem cell therapy on stress urinary incontinence, 7 prospective, single-arm studies were considered (Table 1) [16][17][18][19][20][21][22]. A total of 99 patients were considered.…”

“…Three studies [16][17][18] enrolled patients with isolated stress urinary incontinence, regardless of the triggering cause; two studies included patients with isolated or mixed urinary incontinence [19,20]; one study considered only patients affected by stress urinary incontinence secondary to intrinsic sphincter deficiency [21]; one study enrolled only patients with stress urinary incontinence secondary to urethral hypermobility [22]. The lower abdomen subcutaneous fat was the source of stem cells in three studies [16,18,19], while in other three studies, stem cells were harvested from the muscle tissue [17,21,22]; in one study, the stem cell source was the human cord blood [20]. Stem cell administration procedures included transurethral injection at the proximal urethra via cystoscope, periurethral injection through the skin, and transvaginal periurethral injection.…”

“…No serious adverse effects were reported after SC injection. Reported minor adverse events were 2 cases of hematoma formation during adipose tissue collection [18,19], 3 cases of dysuria that spontaneously resolved a few days Fig. 1 The electronic database search after cell injection [16,18,19], and 2 cases of urinary tract infection [21].…”

“…Different objective outcomes of treatment success were considered, including cough stress test [18,19,22], 24-h pad weight [16][17][18][19], 1-h pad test [21,22], and voiding diary [17]. A negative cough test at 12 months was reported by Kuismanen et al [19] in 3 out of 5 patients (60%) and in 6 out of 10 patients (60%) by Garcia-Arranz et al [18].…”