Bdnf-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury
Lujie Songa、Jianqiang Zhub、Zhiqiang Cuic、Yang Liuc、Qiang Fua、Yue-Min Xua、Hongkai Luc
a Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China；
b Department of Urology, the Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China；
c Department of Urology, Weifang Medical University Affiliated Weifang People’s Hospital, Weifang, Shandong, 261042, China
Corresponding to: Lu-Jie Song, MD. PhD. Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Email: email@example.com ; Telephone: +86-21-64369181; Fax: +86-21-64701361
Introduction：Erectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy.
Aim: To test the hypothesis that intracavernous injection of BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) can ameliorate ED in a rat model of cavernous nerve electrocautery injury (CNEI).
Methods: Forty-two male Sprague-Dawley rats were randomly divided into 4 groups. Group A: Sham operation rats intracavernosally injected with PBS (n=6) , Group B: CNEI rats intracavernosally injected with PBS (n=12), Group C: CNEI rats intracavernosally injected with hUCB-MSCs (n=12), Group D: CNEI rats intracavernosally injected with BDNF-hUCB-MSCs (n=12).
Main Outcome Measures：At week 4, the rats in each group underwent electrostimulation of the cavernous nerves to assess erectile function. Penile tissues were collected for histological examinations (Masson’s trichrome; Immunoflouresecence for S-100 and α-SMA; TUNEL assay). Transmission electron microscopy (TEM) was used to examine the CN distal to the site of injury.
Results: Four weeks after injection, rats which received BDNF-hUCB-MSCs showed the most significant improvement in the ratio of maximal ICP to MAP (ICP/MAP) compared with both the CNEI+hUCB-MSCs and CNEI+PBS animals (P<0.001). Histological examinations showed moderate recovery of S-100 positive nerve fibers, ratio of smooth muscle to collagen and smooth muscle content in the CNEI+hUCB-MSCs group and remarkable recovery in the CNEI+BDNF-hUCB-MSCs group compared to the CNEI+PBS group (P<0.05). Furthermore, there was a significant reduction of apoptotic index in the corpus cavernosum of the CNEI+hUCB-MSCs and CNEI+BDNF-hUCB-MSCs rats compared with the CNEI+PBS animals (P<0.05). By TEM examination, atrophy of myelinated and nonmyelinated nerve fibers was noted in CNEI+PBS group, and significant recovery was observed in two treated groups.
Conclusions: Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration, protect against cells apoptosis and inhibit corpus cavernosum fibrosis after CNEI in a rat model.
Electrocautery injury, Erectile dysfunction(ED), Radical prostatectomy(RP), Brain-derived neurotrophic factor(BDNF), Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)