Co-Overexpressing VEGF and GDNF of ADSCs Ameliorate Erectile Dysfunction by Alleviating Cavernosal Fibrosis in a Rat Model of Bilateral Cavernous Nerve Injury

Abstract

Penile erectile dysfunction (ED) caused by progressive fibrosis of the penis after bilateral cavernous nerve injury (BCNI) is one of the reasons for clinical treatment difficulties. Studies have shown that adipose-derived stem cells (ADSCs) could secrete abundant bioactive substances, which is an important reason for improving ED in BCNI rats. However, more information is needed to clarify what nutrient factors may play a leading role in preparing for effective clinical treatment in the future. The aim of this study was to investigate the effects of Lentivirus-mediated ADSCs overexpression of vascular endothelial growth factor (VEGF) and glial cells derived neurotrophic factors (GDNF) on cavernous nerve (CN) repair and penile erectile dysfunction. Two weeks after BCNI treatment, the CN was electrically stimulated and the erectile function of the rats was measured. Penile tissue and MPG were taken for blind histological analysis or western blotting. Erectile function recovered well in the ADSC-G&V group. ADSC-G&V group significantly increased the content of cavernous endothelial tissue and neuronal nitric oxide synthase, and improved the hypoxia of the corpus cavernosum. MPG from ADSC-G&V group showed morphological changes, including higher expression of NG-F and S100β. Two weeks later, PBS group displayed obviously fibrotic response, while the ADSC-G&V group was significantly inhibited and showed higher penile smooth muscle content and downregulated p-LIMK2/p-Cofilin pathway which was closely related to penile fibrosis after BCNI. Genetically modified ADSCs (GM-ADSCs) of VEGF and GDNF may promote rapid repair of CN and protect the local structure of the penis, thereby recovering erectile function better. Our experiments demonstrated that GM-ADSCs could be used as a means of rapid ameliorate of ED after BCNI, providing new ideas for future clinical treatment. Funding Statement: The study was supported by grants from the National Natural Science Foundation of China (No. 81971378); the Science and Technology Planning Project of Guangdong Province, China (2019B030316011); Sun Yat-Sen University 5010 Program (2015016). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All procedures were approved by the Ethics Committee of the Institutional Animal Care and Use Subcommittee of the Third Hospital of Sun Yat-sen University.