PD8-05 THE PARACRINE EFFECTS OF MESENCHYMAL STEM CELLS STIMULATE THE REGENERATION CAPACITY OF ENDOGENOUS STEM CELLS IN THE REPAIR OF A BLADDER OUTLET OBSTRUCTION-INDUCED OVERACTIVE BLADDER

Abstract

You have accessJournal of UrologyStem Cell Research1 Apr 2014PD8-05 THE PARACRINE EFFECTS OF MESENCHYMAL STEM CELLS STIMULATE THE REGENERATION CAPACITY OF ENDOGENOUS STEM CELLS IN THE REPAIR OF A BLADDER OUTLET OBSTRUCTION-INDUCED OVERACTIVE BLADDER Miho Song, Ji-Youn Chun, Junsoo Park, Ji-Yeon Han, Dong-Myung Shin, Myung-Soo Choo, and Sang Hoon Song Miho SongMiho Song More articles by this author , Ji-Youn ChunJi-Youn Chun More articles by this author , Junsoo ParkJunsoo Park More articles by this author , Ji-Yeon HanJi-Yeon Han More articles by this author , Dong-Myung ShinDong-Myung Shin More articles by this author , Myung-Soo ChooMyung-Soo Choo More articles by this author , and Sang Hoon SongSang Hoon Song More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.799AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The efficacies of current pharmacotherapies using antimuscarinic agents to treat overactive bladder (OAB) are insufficient. To evaluate the therapeutic efficacies of mesenchymal stem-cells (MSCs) and current pharmacotherapies for the treatment of OAB and investigate the therapeutic mechanisms involved in MSC therapy. METHODS OAB was induced in 50 female 6-week-old Sprague Dawley rats by partial bladder-outlet-obstruction (BOO). Ten rats underwent sham operations. Four-weeks after inducing BOO, 50 rats with BOO were divided among 3 groups and received a single transplantation of human adipose-derived MSCs or daily intravenous injections of solifenacin (an antimuscarinic agent) or PBS for 2-weeks. Cystometric parameters, histological examinations, immunostaining for α-SMA, N200, Oct4, and Stella, and the transcriptional activity levels for stemness and stem-cell trafficking genes were measured at 2- and 4-weeks after intervention. RESULTS Both the MSC and solifenacin treatments similarly relieved BOO-induced detrusor overactivity, hypertrophic smooth muscle, and neurological injuries within 2-weeks. In contrast to solifenacin treatment, a single transplantation of MSC improved most OAB parameters to the basal level within 4-weeks. Although the transplanted stem cells were hardly engrafted, the bladders that received MSCs increased the transcription of Oct4, Sox2, and Stella in the experimental rats, which are surrogate markers of pluripotent stem-cells. In addition, MSCs enhanced the expression levels of several genes responsible for stem-cell trafficking. These changes in gene expression were not observed in the solifenacin-treated group. CONCLUSIONS These results indicate that a single transplantation of MSCs can repair bladder function better than current pharmacotherapies due to BOO-induced OAB. Moreover, we suggest that the novel mechanisms for the ¡§paracrine effect¡¨ of MSCs unleash and mobilize primitive endogenous stem-cells, which could not only explain the long-term/stable therapeutic efficacy of MSC therapy but also provide promising new therapies for OAB. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e218 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Miho Song More articles by this author Ji-Youn Chun More articles by this author Junsoo Park More articles by this author Ji-Yeon Han More articles by this author Dong-Myung Shin More articles by this author Myung-Soo Choo More articles by this author Sang Hoon Song More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...