176 INTRAVENOUS MESENCHYMAL STEM CELLS HOME TO THE URETHRA AND FACILITATE RECOVERY FROM STRESS URINARY INCONTINENCE AFTER CHILDBIRTH INJURY VIA LOCAL SECRETION OF PARACRINE FACTORS

Abstract

You have accessJournal of UrologyStem Cell Research1 Apr 2011176 INTRAVENOUS MESENCHYMAL STEM CELLS HOME TO THE URETHRA AND FACILITATE RECOVERY FROM STRESS URINARY INCONTINENCE AFTER CHILDBIRTH INJURY VIA LOCAL SECRETION OF PARACRINE FACTORS Charuspong Dissaranan, Michelle Cruz, Bradley Gill, Levilester Salcedo, Anne Cotleur, Raul Mendieta, Brian Balog, Matt Kiedrowski, Marc Penn, Howard Goldman, and Margot Damaser Charuspong DissarananCharuspong Dissaranan Cleveland, OH More articles by this author , Michelle CruzMichelle Cruz Cleveland, OH More articles by this author , Bradley GillBradley Gill Cleveland, OH More articles by this author , Levilester SalcedoLevilester Salcedo Cleveland, OH More articles by this author , Anne CotleurAnne Cotleur Cleveland, OH More articles by this author , Raul MendietaRaul Mendieta Cleveland, OH More articles by this author , Brian BalogBrian Balog Cleveland, OH More articles by this author , Matt KiedrowskiMatt Kiedrowski Cleveland, OH More articles by this author , Marc PennMarc Penn Cleveland, OH More articles by this author , Howard GoldmanHoward Goldman Cleveland, OH More articles by this author , and Margot DamaserMargot Damaser Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.245AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Vaginal delivery injures the nerves, muscle, and connective tissues responsible for maintaining continence and is a risk factor for the development of Stress Urinary Incontinence (SUI). We have previously demonstrated that stem cell homing cytokine MCP-3, and its receptors, are upregulated in urethral tissue after childbirth injury. Recent studies suggest stem cells may facilitate repair by secreting proteins that have paracrine effects. This study investigated whether stem cells homed to the urethra after childbirth injury and facilitated functional recovery of the urethral sphincter. Specifically, the aim of this study was to determine if intravenous (IV) bone marrow-derived mesenchymal stem cells (MSCs) improved urethral sphincter function compared to local administration of concentrated conditioned media (CCM) containing growth factors produced by the cells. METHODS Age-matched virgin female rats were divided into 6 groups: Vaginal Distension (VD) and IV saline (N=6), VD and IV MSCs (N=7), sham VD and IV saline (N=5), VD and CCM direct sphincter injection (N=5), VD and control media injection (N=4) and sham VD and control media injection (N=5). VD was done as previously described. One hour after injury, 2 million GFP-labeled MSCs or saline was injected via tail vein. MSC conditioned media was concentrated (CCM) and injected directly into the urethra. Outcomes were tested 1 week after injury by simultaneous leak point pressure (LPP) and external urethral sphincter (EUS) electromyography (EMG). Mean frequency and amplitude of 1 sec EUS EMG segments both at rest and during LPP were analyzed. Urethras and vaginas were harvested and imaged ex-vivo for MSCs GFP. RESULTS Continence (LPP) was significantly reduced in VD rats treated with saline or control media compared to sham VD but not in those given IV MSCs or CCM. EUS EMG frequency and amplitude, as well as LPP were significantly decreased in all VD rats, regardless of treatment, compared to sham VD. GFP imaging showed increased fluorescence, indicating MSCs, in the urethra and vagina of VD rats receiving IV MSCs. CONCLUSIONS IV MSCs home to the urethra and facilitate recovery of continence after childbirth injury, but not by increasing EUS function. Therefore, improved LPP likely results from the local secretion of paracrine factors by MSCs. The exact mechanism of action leading to restored continence requires further investigation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byGill B, Damaser M, Vasavada S and Goldman H (2018) Stress Incontinence in the Era of Regenerative Medicine: Reviewing the Importance of the Pudendal NerveJournal of Urology, VOL. 190, NO. 1, (22-28), Online publication date: 1-Jul-2013. Volume 185Issue 4SApril 2011Page: e73 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Charuspong Dissaranan Cleveland, OH More articles by this author Michelle Cruz Cleveland, OH More articles by this author Bradley Gill Cleveland, OH More articles by this author Levilester Salcedo Cleveland, OH More articles by this author Anne Cotleur Cleveland, OH More articles by this author Raul Mendieta Cleveland, OH More articles by this author Brian Balog Cleveland, OH More articles by this author Matt Kiedrowski Cleveland, OH More articles by this author Marc Penn Cleveland, OH More articles by this author Howard Goldman Cleveland, OH More articles by this author Margot Damaser Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...