MP43-12 INHIBITION OF PHOSPHODIESTERASE-5 IMPROVES THERAPEUTIC EFFICACY OF ADIPOSE-DERIVED STEM CELLS FOR ERECTILE DYSFUNCTION IN DIABETIC RATS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2014MP43-12 INHIBITION OF PHOSPHODIESTERASE-5 IMPROVES THERAPEUTIC EFFICACY OF ADIPOSE-DERIVED STEM CELLS FOR ERECTILE DYSFUNCTION IN DIABETIC RATS Jun Yang, Tao Wang, Yan Zhang, Li Zhuan, Hua Xu, Shao-Gang Wang, Ji-Hong Liu, and Zhang-Qun Ye Jun YangJun Yang More articles by this author , Tao WangTao Wang More articles by this author , Yan ZhangYan Zhang More articles by this author , Li ZhuanLi Zhuan More articles by this author , Hua XuHua Xu More articles by this author , Shao-Gang WangShao-Gang Wang More articles by this author , Ji-Hong LiuJi-Hong Liu More articles by this author , and Zhang-Qun YeZhang-Qun Ye More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1169AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Adipsoe-derived stem cells (ADSCs) have been recently considered promising therapy for erectile dysfunction (ED). However, the therapeutic efficacy of ADSCs-based therapy remains to be improved. This study was designed to determine whether inhibition of phosphodiesterase-5 (PDE5) with a silencing vector in adipose-derived stem cells (ADSCs) would improve stem cell therapy for erectile dysfunction in diabetic rats, and to investigate its underlying mechanisms. Methods A PDE5 siRNA was incorporated into lentiviral vectors and then transduced into ADSCs. Cells were evaluated for PDE5 mRNA and protein expression, and cGMP level at different time points. 3 days after transduction, the ADSCs-conditioned medium was collected to determinate the level of IGF-1 and VEGF. A streptozotocin-induced diabetes rat model was established and used for comparative analysis of 2-week treatment regimens with ADSCs or PDE5 siRNA modified ADSCs. At 2-week post-transplantation, all the rats were analyzed for erectile function, cavernous IGF-1 and VEGF levels, and penile histology. Results Compared to ADSCs transfected with negative control siRNA vector (ADSCs plus vector), ADSCs showed a significant decrease in PDE5 expression and elevated cGMP level at 3d, 5d, 7d, 10d and 14d after transfection with PDE5 siRNA vector (ADSCs plus siRNA) (P<0.05). ADSCs plus siRNA could secrete more IGF-1 and VEGF in culture medium than those of ADSCs and ADSCs plus vector (P<0.05). Compared to normal control rats (2.5v 0.711±0.059, n=10), the Max ICP/MAP was found to be markedly decreased in untreated diabetic rats (2.5v 0.355±0.046, n=10) (P<0.05). The corpus cavernosum of untreated diabetic rats showed decreased IGF-1 and VEGF levels, and contents of cavernous smooth muscle and endothelium compared to normal control rats (P<0.05). Diabetic rats injected with ADSCs plus siRNA (2.5v 0.665±0.052, n=10) showed enhanced erectile function as compared to ADSCs (2.5v 0.522±0.043, n=10) or ADSCs plus vector (2.5v 0.515±0.038, n=10) treatment (P<0.05), which also improved erectile function of diabetic rats (P<0.05). The benefits of ADSCs plus siRNA therapy were associated with significantly increased IGF-1 and VEGF levels, and contents of cavernous smooth muscle and endothelium in penile tissues as compared with ADSCs or ADSCs plus vector treatment (P<0.05). Conclusions Inhibition of PDE5 can be a powerful approach to improve stem cell therapy for erectile dysfunction in diabetic rats. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e481 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Jun Yang More articles by this author Tao Wang More articles by this author Yan Zhang More articles by this author Li Zhuan More articles by this author Hua Xu More articles by this author Shao-Gang Wang More articles by this author Ji-Hong Liu More articles by this author Zhang-Qun Ye More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...