259 INTRACAVERNOSAL STEM CELL THERAPY COMBINED WITH ORAL TADALAFIL ADMINISTRATION PRESERVES ERECTILE FUNCTION AFTER CAVERNOUS NERVE INJURY IN RATS

Abstract

You have accessJournal of UrologyStem Cell Research1 Apr 2013259 INTRACAVERNOSAL STEM CELL THERAPY COMBINED WITH ORAL TADALAFIL ADMINISTRATION PRESERVES ERECTILE FUNCTION AFTER CAVERNOUS NERVE INJURY IN RATS Juan I. Martínez-Salamanca, Mercedes Zurita, Claudio Martínez-Ballesteros, Eduardo Martínez-Salamanca, Argentina Fernández, Pedro Cuevas, Jesús Vaquero, Joaquín Carballido, Carla Costa Costa, and Javier Angulo Juan I. Martínez-SalamancaJuan I. Martínez-Salamanca Madrid, Spain More articles by this author , Mercedes ZuritaMercedes Zurita Madrid, Spain More articles by this author , Claudio Martínez-BallesterosClaudio Martínez-Ballesteros Madrid, Spain More articles by this author , Eduardo Martínez-SalamancaEduardo Martínez-Salamanca Madrid, Spain More articles by this author , Argentina FernándezArgentina Fernández Madrid, Spain More articles by this author , Pedro CuevasPedro Cuevas Madrid, Spain More articles by this author , Jesús VaqueroJesús Vaquero Madrid, Spain More articles by this author , Joaquín CarballidoJoaquín Carballido Madrid, Spain More articles by this author , Carla Costa CostaCarla Costa Costa Porto, Portugal More articles by this author , and Javier AnguloJavier Angulo Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1641AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Since the treatment of erectile dysfunction secondary to radical prostatectomy still remains as an outstanding challenge, this work was aimed to evaluate the efficacy of dual targeted strategy to promote cavernosal tissue preservation using systemic PDE5 inhibition and local stem-cell therapy in a rat model of cavernous nerve (CN) injury. METHODS Bilateral CN crush injury (BCNI) was produced in anesthetized male Wistar rats. Tadalafil was orally administered at 5 mg/kg/day dose, Bone marrow-derived mesenchymal stem cells (BMSC) were obtained from donor rats and in vitro expanded and characterized before intracavernosal implantation by means of an automated microinjector pump. Ex vivo function of corpus cavernosum (CC) and In vivo intracavernosal pressure (ICP) responses to CN electrical stimulation (CNES) were evaluated 4 weeks after BCNI. Cavernosal apoptosis was determined by TUNEL assays. RESULTS In CC from BCNI rats, neurogenic contractions driven by adrenergic system were enhanced while nitrergic relaxations were markedly impaired. Oral tadalafil, BMSC or combined strategy improved neurogenic relaxations and prevented cavernosal apoptosis (Table). Relaxations of CC to carbachol or sodium nitrroprusside were not altered by BCNI or any of the treatments. BCNI resulted in marked reduction of erectile responses to CNES which were partially recovered by treatment with tadalafil or by intracavernosal implantation of BMSC. The complete recovery of erectile function was only achieved when both treatments were combined (Table). CONCLUSIONS BCNI did not impair endothelial or smooth muscle relaxation of CC but selectively blunted nitrergic relaxation which was improved by oral tadalafil and intracavernosal BMSC. Erectile function was recovered only when both therapies were combined. These results support the use of dual therapeutic approaches, cell therapy and oral PDE5 inhibitors, for recovering erectile function in patients undergoing radical prostatectomy. sham BCNI BCNI+ TAD BCNI+ BMSC BCNI+ TAD+BMSC n 9 9 5 6 5 Emax adrenergic (% of K) 102.9±34.2 214.5±25.0⁎ 117.8±38.2† 218.8±47.3 157.5±20.3 Emax nitrergic (%) 64.4±10.0 20.4±5.8⁎ 36.3±19.1 39.3±9.9 45.4±6.5† Apoptotic cells/field 1.6±0.4 15.8±0.8⁎⁎⁎ 4.0±0.7⁎††† 5.5±0.8⁎⁎††† 4.6±1.0⁎††† max ICP (% of sham) 100.0±6.3 45.9±5.7⁎⁎⁎ 76.3±11.1† 62.2±14.8⁎ 92.4±4.8†† ⁎ p< 0.05, ⁎⁎ p<0.01 ⁎⁎⁎ p<0.001 vs. sham, † p<0.05, †† p<0.01, ††† p<0.001 vs. BCNI. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e106 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan I. Martínez-Salamanca Madrid, Spain More articles by this author Mercedes Zurita Madrid, Spain More articles by this author Claudio Martínez-Ballesteros Madrid, Spain More articles by this author Eduardo Martínez-Salamanca Madrid, Spain More articles by this author Argentina Fernández Madrid, Spain More articles by this author Pedro Cuevas Madrid, Spain More articles by this author Jesús Vaquero Madrid, Spain More articles by this author Joaquín Carballido Madrid, Spain More articles by this author Carla Costa Costa Porto, Portugal More articles by this author Javier Angulo Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...