524 CELL THERAPY FOR THE TREATMENT OF URINARY SPHINCTER NERVE DECENTRALIZATION IN FEMALE NONHUMAN PRIMATES (2012)

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Incontinence - Evaluation & Therapy I1 Apr 2012524 CELL THERAPY FOR THE TREATMENT OF URINARY SPHINCTER NERVE DECENTRALIZATION IN FEMALE NONHUMAN PRIMATES Sherif Badra, Gordon McLorie, Sherif Mourad, James Yoo, and Koudy Williams Sherif BadraSherif Badra winston salem, NC More articles by this author , Gordon McLorieGordon McLorie winston salem, NC More articles by this author , Sherif MouradSherif Mourad Cairo, Egypt More articles by this author , James YooJames Yoo winston salem, NC More articles by this author , and Koudy WilliamsKoudy Williams winston salem, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.596AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The concept of cell therapy for urinary incontinence (UI) is the subject of ongoing research and clinical trials in a number of centers. The pathogenesis of UI is varied but includes sphincteric nerve damage during - and subsequent muscle loss after - delivery. Our objective was to utilize a female nonhuman primate model of sphincter nerve (pudendal) damage to determine if and to what extent injection of skeletal muscle precursor cells restored structure and function in damaged urinary sphincter. METHODS Twenty premenopausal female cynomolgus monkeys were used in this study and were divided into three groups: control (n=4), sphincter deficiency only (n=8) and sphincter deficiency + autologous skeletal muscle precursor cell (skMPC) injection (n=8). Sphincteric damage (decentralization) was created by pudendal nerve transection on both sides of the urethra. Muscle biopsy was taken from quadriceps of monkeys where skMPC were isolated, characterized, expanded and labeled with lenti-GFP. In the treated group, 5 million cells suspended in 2ml saline were injected in multiple locations around the sphincter. In vivo urodynamic evaluations were done prior to, and at 1 and 3 months post-injury. Urinary sphincters were assessed histologically for structure and characterization of the injected cells. RESULTS The injured group showed marked decrease in urethral sphincteric pressure by 30% at rest, and by 40% in response to pudendal nerve stimulation, decreased muscle content, contrast CT cystourethrography indicated widening of the sphincteric outflow tract and decreased expression of skeletal muscle and neuronal markers. Conversely, there was an improvement in sphincteric pressures in the treated group; restoration of outflow tract diameter; increased muscle content and expression of muscle markers by injected cells with adjacent expression of neuronal markers. CONCLUSIONS SkMPC therapy promoted both structural and functional regeneration of the decentralized urinary sphincter in a female nonhuman primate model that shares with human females similar anatomy and physiology of the genitourinary urinary tract. As such, this study provides translational evidence that cell therapy may be of use to treat this form of UI. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e215 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sherif Badra winston salem, NC More articles by this author Gordon McLorie winston salem, NC More articles by this author Sherif Mourad Cairo, Egypt More articles by this author James Yoo winston salem, NC More articles by this author Koudy Williams winston salem, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...