Stress urinary incontinence (SUI) is a major health problem that has many social and economic impacts, so we evaluated the long-term effect of locally and systemically administrated adipose tissue-derived mesenchymal stem cells (ADMSCs) on the treatment of SUI-induced in a rat model.

Thirty-two female Sprague-Dawley rats were randomly allocated into 4 groups (8 rats each); control, SUI, local ADMSCs and systemic ADMSCs groups. SUI was induced by vaginal dilatation of the rats via inflating the balloon of a urethral catheter with 5 mL sterile saline in the vagina for 8 hours. Rats then received 0.9% saline, local ADMSCs treatment (periurethal injection at 5 and 7 o’clock positions of the vesico-urethral junction) and systemic ADMSCs treatment (injection in the tail vein) in SUI, local and systemic ADMSCs groups, respectively for 4 weeks. Urodynamic study in terms of abdominal leak point pressure (ALPP), threshold pressure (TP) and bladder capacity (BC) was performed. Rats were then sacrificed and their periurethral regions were sent for routine histopathological examination.

There was significant improvement in the results of the urodynamic study in terms of ALPP, TP and BC after administration of either local or systemic ADMSCs for 4 weeks relative to SUI group (Figure 1). There was also significant evidence of regeneration of the muscle layers in the periurethral regions with less inflammation and fibrosis in local and systemic ADMSCs groups compared to SUI group (Figure 2). Apart from BC, the locally administrated ADMSCs significantly provided more favorable effects than the systemically administrated ADMSCs.

SUI resulted in significant damage of the muscle layers in the periurethral regions with subsequent inflammation and fibrosis. SUI group showed significant decrease in the urodynamic parameters; ALPP, TP and BC compared to the control group. However, ADMSCs administration significantly regenerated the affected muscle layers in the periurethral regions after induction of SUI. The routine histopathological examination of the periurethral regions revealed less inflammation and less fibrosis in both local and systemic ADMSCs groups relative to SUI group. Local and systemic administration of ADMSCs for 4 weeks also showed significant improvement in the results of the urodynamic study in terms of ALPP, TP and BC compared to SUI group. Apart from BC, local administration of ADMSCs offered more significant improvement in the morphological and urodynamic dysfunctions than the systemic administration of ADMSCs.

Long-term administration of ADMSCs either locally or systemically in the periurethral regions in SUI improves the morphological and urodynamic dysfunctions of the affected urethral sphincters.