Adipose-derived stem cells modified by BDNF gene rescue erectile dysfunction after cavernous nerve injury

Cavernous nerve injury is the main cause of erectile dysfunction following radical prostatectomy. The recovery of erectile function following radical prostatectomy remains challenging. Our previous studies found that injecting adipose-derived stem cells (ADSCs) into the cavernosa could repair the damaged cavernous nerves, but the erectile function of the treated rats could not be restored to a normal level. We evaluated the efficacy of ADSCs infected with a lentiviral vector encoding rat brain-derived neurotrophic factor (lenti-rBDNF) in a rat model of cavernous nerve injury. The rats were equally and randomly divided into four groups. In the control group, bilateral cavernous nerves were isolated but not injured. In the bilateral cavernous nerve injury group, bilateral cavernous nerves were isolated and injured with a hemostat clamp for 2 minutes. In the ADSC_GFP and ADSC_rBDNF groups, after injury with a hemostat clamp for 2 minutes, rats were injected with ADSCs infected with lenti-GFP (1 × 10⁶ in 20 μL) and lenti-rBDNF (1 × 10⁶ in 20 μL), respectively. Erectile function was assessed 4 weeks after injury by measuring intracavernosal pressures. Then, penile tissues were collected for histological detection and western blot assay. Results demonstrated that compared with the bilateral cavernous nerve injury group, erectile function was significantly recovered in the ADSC_GFP and ADSC_rBDNF groups, and to a greater degree in the ADSC_rBDNF group. Neuronal nitric oxide synthase content in the dorsal nerves and the ratio of smooth muscle/collagen were significantly higher in the ADSC_rBDNF and ADSC_GFP groups than in the bilateral cavernous nerve injury group. Neuronal nitric oxide synthase expression was obviously higher in the ADSC_rBDNF group than in the ADSC_GFP group. These findings confirm that intracavernous injection with ADSCs infected with lenti-rBDNF can effectively improve erectile dysfunction caused by cavernous nerve injury. This study was approved by the Medical Animal Care and Welfare Committee of Wuhan University, China (approval No. 2017-1638) on June 20, 2017.