Treatment of stress urinary incontinence with adipose tissue-derived stem cells.
OBJECTIVE
Effective treatment for stress urinary incontinence (SUI) is lacking. This study investigated whether transplantation of adipose tissue-derived stem cells (ADSC) can treat SUI in a rat model.


METHODS
Rats were induced to develop SUI by postpartum vaginal balloon dilation and bilateral ovariectomy. ADSC 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 a control. Twelve rats received urethral injection of EdU-labeled ADSC and six rats received intravenous injection of BrdU-labeled ADSC through the tail vein. Four weeks later, urinary voiding function was assessed by conscious cystometry. The rats were then killed and their urethras harvested for tracking of ADSC and quantification of elastin, collagen and smooth muscle contents.


RESULTS
Cystometric analysis showed that eight out 10 rats in the control group had abnormal voiding, whereas four of 12 (33.3%) and two of six (33.3%) rats in the urethra-ADSC and tail vein-ADSC groups, respectively, had abnormal voiding. Histologic 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.


CONCLUSIONS
Transplantation of ADSC via urethral or intravenous injection is effective in the treatment and/or prevention of SUI in a pre-clinical setting.
Lin
Guiting
G
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, California, USA.
Wang
Guifang
G
Banie
Lia
L
Ning
Hongxiu
H
Shindel
Alan W
AW
Fandel
Thomas M
TM
Lue
Tom F
TF
Lin
Ching-Shwun
CS
D000273:Adipose Tissue / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D000818:Animals; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007275:Injections, Intravenous; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D007744:Obstetric Labor Complications / Q000503:physiopathology / Q000628:therapy; D010052:Ovariectomy; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D014521:Urethra / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D014550:Urinary Incontinence, Stress / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D014554:Urination / Q000502:physiology; D014621:Vagina / Q000293:injuries / Q000601:surgery
D001973:Bromodeoxyuridine