AB306. SPR-33 Systemic treatment of stress urinary incontinence with human urine-derived stem cells

Abstract

Objective

Stem cell based therapy has emerged as a promising treatment alternative for stress urinary incontinence (SUI). Human urine-derived stem cells (USCs) have no risk from biopsy and therefore may be a better option than other adult stem cells. Possible therapeutic mechanisms of action of stem cells are homing of cells to areas in need of repair and secretion of bioactive paracrine factors acting systemically as well as locally. We hypothesized that USCs or their secretome alone would promote functional recovery in a rodent model of female SUI even when given systemically.

Methods

Thirty two-female Sprague-Dawley rats were randomized into three groups and underwent vaginal distension (VD) followed by intraperitoneal (ip) delivery of USCs (VD + USCs) VD and ip delivery of saline as a vehicle control, or sham VD with ip saline. Three additional groups (32 rats) were utilized to investigate if factors secreted by USCs alone facilitate recovery from VD: concentrated conditioned media (CCM) from USCs given ip after VD, concentrated control media (CM) given ip after VD, and CM given ip after sham VD. All treatments were given 1 hour after VD or sham VD. CCM was generated by incubating confluent USCs in serum-free media for 24 hours. Cultured supernatant was then extracted, washed, and concentrated to form CCM. One week after injury, treatment efficacy was assessed by measurement of leak point pressure (LPP), and qualitative anatomical assessment of the urethra. Quantitative data were analyzed by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc tests with P<0.05 indicating a significant difference.

Results

LPP significantly increased after VD in rats treated with USCs or CCM, compared to animals that received saline, but not significantly different from sham VD. Collagen infiltration of striated muscle in the external urethral sphincter, along with substantial muscle fiber attenuation and disruption of the striated muscle layers were noted, as has been observed previously in this model. External urethral sphincter structure was greatly improved with USC implantation, and was more similar to that of sham-injured animals than injured rats treated with saline. Elastin fibers in VD + USCs and VD + CCM animals were long, thickened, and mostly oriented compared to the short, thin, and disoriented fibers in VD + saline and VD + CM animals. No human USCs were found in the region of urethra.

Conclusions

Ip injection of USCs and their secretions facilitate recovery from SUI in a rat model, likely via systemic and paracrine mechanisms. Elastogenesis may play a role in recovery of urethral function. USCs represent an attractive, alternate stem cell source with no biopsy risk to target the underlying pathophysiology in SUI.

Funding Source(s)

NIH NIDDK R56 DK100669-01A1, the Research Projects Committee of the Cleveland Clinic, and the Rehabilitation R&D Service of the Department of Veterans Affairs