Treatment of Stress Urinary Incontinence with Adipose Tissue- Derived Stem Cells

National Institutes of Health



Cytotherapy. 2010 ; 12(1): 88–95. doi:10.3109/14653240903350265.

Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-0738, USA

Guiting Lin, Guifang Wang, Lia Banie, Hongxiu Ning, Alan W. Shindel, Thomas M. Fandel,Tom F. Lue, and Ching-Shwun Lin



Background—Effective treatment for stress urinary incontinence (SUI) is lacking. This study investigates whether transplantation of adipose tissue-derived stem cells (ADSCs) can treat SUI in a rat model.

Methods—Rats were induced to develop SUI by postpartum vaginal balloon dilation and bilateral ovariectomy. ADSCs were isolated from the peri-ovary fat, examined for stem cell properties, and labeled with thymidine analog BrdU or EdU. Ten rats received urethral injection of saline as control. Twelve rats received urethral injection of EdU-labeled ADSCs and 6 rats received intravenous injection of BrdU-labeled ADSCs through tail vein. Four weeks later, urinary voiding function was assessed by 4-channel conscious cystometry. The rats were then sacrificed and their urethras harvested for tracking of ADSCs and for quantification of elastin, collagen, and smooth muscle contents.

Results—Cystometric analysis showed that 8 out 10 rats in the control group had abnormal voiding whereas 4 of 12 (33.3%) and 2 of 6 (33.3%) rats in the Urethra-ADSC group and the Tail Vein- ADSC group, respectively, had abnormal voiding. Histological analysis showed that the ADSC- treated groups had significantly higher elastin content than the control group, and, within the ADSC- treated groups, rats with normal voiding pattern also had significantly higher elastin content than rats with voiding dysfunction. ADSC-treated, normal voiding rats had significantly higher smooth muscle content than control or ADSC-treated rats with voiding dysfunction.



While the cystometric and histological data suggest the therapeutic potential of ADSCs, it remains unknown how the transplanted ADSCs improved urethral function. In the Tail Vein- ADSC group the transplanted cells migrated to the injured urethra possibly on cue of homing factors such as SDF-1, as ADSCs have been shown to express the SDF-1 receptor CXCR4 and migrate to SDF-1 in cell migration assays [31]. Thus, we consider the migration of ADSCs toward the injured urethra as one of the steps through which voiding dysfunction was mitigated. Once in the urethra, the tail vein-injected ADSCs were likely able to perform functions similar to ADSCs transplanted directly in the urethra. As detected by EdU-staining, the urethrally injected ADSCs were largely localized in the submucosa (Fig. 4C) and a few of the EdU- positive nuclei appeared to reside within cells expressing -SMA (Fig. 4D). Thus, it appears that a small fraction of the transplanted ADSCs might have differentiated into smooth muscle cells. However, since the great majority of the transplanted ADSCs appeared to remain undifferentiated, their therapeutic effects were likely mediated by trophic factors that promote host tissue regeneration. This trophic mechanism has been proposed for ADSCs [32] and has been discussed in reviews of mesenchymal stem cells in general [33,34]. Thus, we consider that urethral or intravenous injection of ADSCs can mitigate SUI by a trophic factor mechanism that modifies both cellular and extracellular elements of the urethra.


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