MP86-14 TREATMENT OF DIABETES MELLITUS-INDUCED ERECTILE DYSFUNCTION USING ENDOTHELIAL PROGENITOR CELLS GENETICALLY MODIFIED WITH HUMAN TELOMERASE REVERSE TRANSCRIPTASE

Abstract

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology I1 Apr 2016MP86-14 TREATMENT OF DIABETES MELLITUS-INDUCED ERECTILE DYSFUNCTION USING ENDOTHELIAL PROGENITOR CELLS GENETICALLY MODIFIED WITH HUMAN TELOMERASE REVERSE TRANSCRIPTASE Yan Zhang, Tao Wang, Jun Yang, Rui Li, Zhi Chen, Shaogang Wang, Jihong Liu, and Zhangqun Ye Yan ZhangYan Zhang More articles by this author , Tao WangTao Wang More articles by this author , Jun YangJun Yang More articles by this author , Rui LiRui Li More articles by this author , Zhi ChenZhi Chen More articles by this author , Shaogang WangShaogang Wang More articles by this author , Jihong LiuJihong Liu More articles by this author , and Zhangqun YeZhangqun Ye More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2322AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Erectile dysfunction (ED) is one of the most common complications of diabetes mellitus (DM). The efficacy of treatments for diabetes mellitus-induced erectile dysfunction (DMED) is quite poor, and stem cell therapy is emerging as a useful method. This study evaluated the possibility and mechanisms of DMED treatment with endothelial progenitor cells (EPCs) genetically modified to express human telomerase reverse transcriptase (hTERT). METHODS Rat EPCs were isolated and transfected with hTERT (EPCs-hTERT). Proliferation capacity, intracellular reactive oxygen species, paracrine character and resistance to oxidative stress of EPCs-hTERT were assessed in vitro. Diabetes was induced via an intraperitoneal injection of streptozotocin. Twenty-four male DMED rats were subjected to four treatments: DMED (DMED group), EPCs (EPCs group), EPCs transfected with control lentivirus (EPC-control group) and EPCs-hTERT (EPCs-hTERT group). A group of health rats were used as a normal control group. Intracavernosal pressure (ICP) was measured using electrical stimulation for each group after 2 weeks of EPC injections. Masson's trichrome staining was performed to determine collagen content in penile tissues. The degree of apoptosis was assessed using western blotting analysis for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway was detected. RESULTS EPCs-hTERT secreted more growth factors than EPCs and EPCs-control. EPC resistance to oxidative stress and proliferation was dramatically improved by hTERT transfection. The ICP/mean arterial pressure (MAP) ratio induced by electrical stimulation was markedly increased in the EPCs-hTERT group compared with the EPCs and EPCs-control group. Immunofluorescence demonstrated increased cell survival in penile tissues after EPCs-hTERT implantation. The smooth muscle/collagen ratio was markedly increased in the EPCs-hTERT group. TGF-β1 and p-Smad expression decreased significantly in DMED rats after EPCs-hTERT treatment. The degree of apoptosis in penile tissues of the EPCs-hTERT group was considerably reduced, as demonstrated by the decreased Bax/Bcl-2 ratio. NOS expression and NO and cGMP concentrations increased significantly in the EPCs-hTERT group. CONCLUSIONS The enhanced paracrine effect, resistance to oxidative stress and EPCs-hTERT proliferation contributed to the improvement of erectile function in DMED rats. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1111 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yan Zhang More articles by this author Tao Wang More articles by this author Jun Yang More articles by this author Rui Li More articles by this author Zhi Chen More articles by this author Shaogang Wang More articles by this author Jihong Liu More articles by this author Zhangqun Ye More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...