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• W2795448957 abstract "You have accessJournal of UrologyStem Cell Research: Stem Cell Research I1 Apr 2018PD33-03 CELL MOBILIZATION AS A TREATMENT STRATEGY FOR CHRONIC URINARY INCONTINENCE James Koudy Williams, Doug Shankle, Frank Marini, Shannon Lankford, Gopal Badlani, and Karl-Erik Andersson James Koudy WilliamsJames Koudy Williams More articles by this author , Doug ShankleDoug Shankle More articles by this author , Frank MariniFrank Marini More articles by this author , Shannon LankfordShannon Lankford More articles by this author , Gopal BadlaniGopal Badlani More articles by this author , and Karl-Erik AnderssonKarl-Erik Andersson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1558AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The role of injected stem cells in regeneration of urinary tissue structure and function is unclear. This study was to explore cell mobilization as a major mechanism underlying stem cell efficacy is tissue regeneration. METHODS Adult female cynomolgus monkeys (NHPs) with induced chronic urinary sphincter deficiency and partial bone marrow transplantation with GFP-transduced cells, underwent sphincter injections of autologous M-cherry-transduced skeletal muscle precursor cells (skMPCs) (n=6), or the cell mobilizing chemokine CXCL12 (n=6). Maximal resting and pudendal nerve stimulated urethral pressures (MUP) were measured monthly for 6 months, followed by quantitative multiplex/multispectral immunohistochemical analysis of the urinary sphincter complex. RESULTS Injections of CXCL12, but not skMPCs, restored resting and pudendal nerve stimulated MUP values to baseline levels. There were few (< 2% of nucleated cells) skMPCs seen in the sphincter complex 6 months post injection. CXCL12, but not skMPC, injections increased the muscle content (smooth and striated), innervation (somatic and adrenergic) and vascularization to that measured in normal urinary sphincters (n=6 NHPs). Importantly, CXCL12, but not skMPC, injections resulted in greater numbers of BMCs found in the sphincter complex. These BMC origin cells were found in all areas of the sphincter complex (muscle, sub-mucosa and urothelium). They were co-localized in pudendal and adrenergic innervation and were found and integrating with and expressing endothelial markers within the neovascularization. They also expressed markers for smooth and striated muscle cells and expressed markers for muscle cells and urothelium. CONCLUSIONS In contrast with results of preclinical studies reporting almost complete restoration of sphincter function in animal models of acute sphincter dysfunction, cell therapies have been only modestly effective in treating women with chronic stress urinary incontinence (SUI). This could be associated with minimal integration and cell mobilization properties of cells in chronic SUI. In contrast, stimulation of cell mobilization (in this case with CXCL12) may represent a viable treatment target for restoring urological tissues in women with chronic urinary sphincter dysfunction. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e651 Advertisement Copyright & Permissions© 2018MetricsAuthor Information James Koudy Williams More articles by this author Doug Shankle More articles by this author Frank Marini More articles by this author Shannon Lankford More articles by this author Gopal Badlani More articles by this author Karl-Erik Andersson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2795448957 title "PD33-03 CELL MOBILIZATION AS A TREATMENT STRATEGY FOR CHRONIC URINARY INCONTINENCE" @default.
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