105 Does Neoadjuvant Androgen Deprivation Therapy Impact Erectile Function Recovery Post-Radical Prostatectomy?

Abstract

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 EPCshTERT group. TGF-b1 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 EPCshTERT group. CONCLUSIONS: The enhanced paracrine effect, resistance to oxidative stress and EPCs-hTERT proliferation contributed to the improvement of erectile function in DMED rats.