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Treatment of stress urinary incontinence with adipose tissue-derived stem cells
Authors:Guiting Lin  Guifang Wang  Lia Banie  Hongxiu Ning  Alan W Shindel  Thomas M Fandel  Tom F Lue  Ching-Shwun Lin
Institution:1. Department of Obstetrics and Gynecology, Turku University and Salo Regional Hospital, Turku, Finland;2. Department of Obstetrics and Gynecology, Turku University Hospital, Turku, Finland;3. Department of Obstetrics and Gynecology, Lohja Hospital and Turunmaa Hospital, Turku, Finland;4. Turku University, Turku, Finland;1. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA;2. Program in Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA;3. Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;4. Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;5. Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA;6. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA;7. Department of Veterans Affairs, Tennessee Valley Health Authority, Vanderbilt University, Nashville, TN 37212, USA;1. Department of Gynecology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China;2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, PR China;3. Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou, Zhejiang 310058, PR China;4. Center for Stem Cells and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China;5. Zhejiang Xinyue Biotechnology Co. Ltd., Hangzhou, Zhejiang 311121, PR China;1. Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA, USA;2. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA;3. Department of Obstetrics, Gynecology, Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA;1. Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA;2. Institute for Stem Cell Biology & Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA;3. Department of Applied Physics, Stanford University, Stanford, CA, USA;4. Maternity and Children''s Healthcare Hospital of Shenzhen City, Shenzhen, China;5. Guangzhou Medical University, Guangzhou, China;3. From the Division of Allergy, Pulmonary, and Critical Care, University of Wisconsin, Madison, Wisconsin 53792 and;4. Section of Pulmonary and Critical Care Medicine, Department of Medicine, the University of Chicago, Chicago, Illinois 60637
Abstract:Background aimsEffective 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.MethodsRats 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.ResultsCystometric 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.ConclusionsTransplantation of ADSC via urethral or intravenous injection is effective in the treatment and/or prevention of SUI in a pre-clinical setting.
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