高表達BNDF的人臍血間充質幹細胞移植治療大鼠海綿體神經電凝損傷的實驗研究
宋魯傑a、朱建強b、崔志強c、劉陽c、傅強a、徐月敏a、盧洪凱c
a 上海交通大學附屬第六人民醫院泌尿外科，上海，200233，中國；
b 天津醫科大學第二醫院泌尿外科，天津泌尿外科研究所，天津，300211，中國；
c 濰坊醫學院附屬濰坊市人民醫院泌尿外科，山東濰坊，261042，中國
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: ljsong@sjtu.edu.cn ; 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.
Keywords
Electrocautery injury, Erectile dysfunction(ED), Radical prostatectomy(RP), Brain-derived neurotrophic factor(BDNF), Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs)