Therapeutic Potential of Adipose-derived Stem Cell-based Microtissues in a Rat Model of Stress Urinary Incontinence

Abstract

To examine the potential and mechanism of 3-dimensional cultures of adipose-derived stem cells (ADSCs) in the treatment of stress urinary incontinence (SUI) in a rat model simulating menopause combined with preceding childbirth injury. ADSCs were used to generate microtissues (MTs) with a hanging drop method. Forty-eight postpartum Sprague-Dawley rats were developed as SUI models after 4 hours of vagina dilation followed by bilateral ovariectomy. Ten rats that underwent sham ovariectomy without vagina dilation served as the control group. The SUI rats were divided into 3 groups and received urethral injection of phosphate-buffered saline, ADSCs, and MTs. Specimens were harvested for histology examination and ADSCs tracking at days 1, 3, 7, and 28 (n = 3) postinjection. At day 28, the remaining rats were examined for voiding function. Western blot, immunofluorescence, and immunohistochemistry staining were performed to examine histological changes and cytokine expression. The voiding function and histopathological structures were better recovered in the MT group than in the ADSC group. Compared with ADSCs, MTs express higher level of vascular endothelial growth factor and TNFα-stimulated gene/protein 6 in vitro, and represented a higher retention rate in vivo. Urethral injection of MTs better restored voiding function than ADSCs.