title: BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury.
abstract: OBJECTIVE
  Erectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy. We hypothesize 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 four groups: sham + PBS (n = 6), CNEI + PBS (n = 12), CNEI + hUCB-MSCs (n = 12) and CNEI + BDNF-hUCB-MSCs (n = 12). At day 28 post-surgery, erectile function was examined and specimens were harvested for histology. Immunofluorescence staining, Masson's trichrome staining and transmission electron microscopy were performed to determine the structural changes in corpus cavernosum. Cells that are injected into penis were labeled by BrdU and tracked by immunofluorescence staining. Three days post-surgery, the concentration of BDNF protein in penile tissues was measured by Western blotting.
  
  
  RESULTS
  Rats intracavernosally injected with BDNF-hUCB-MSCs showed the most significant improvement in the ratio of maximal ICP to MAP (ICP/MAP). Histological examinations showed moderate recovery of nNOS-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. By TEM examination, atrophy of myelinated and non-myelinated nerve fibers was noted in CNEI + PBS group and significant recovery was observed in two treated groups. There were more BrdU-positive cells in the BDNF-hUCB-MSCs group than in the hUCB-MSCs group both in the penis and in the MPG. Three days post-surgery, the concentration of BDNF protein in penile tissues in BDNF-hUCB-MSCs group was much higher than in other groups.
  
  
  CONCLUSIONS
  Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration and inhibit corpus cavernosum fibrosis after CNEI in a rat model.
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Lujie
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Urology, the Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Burn and Plastic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, 197 Ruijin Second Road, Shanghai, 200025, China. zhangxiongsh@foxmail.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.|Department of Urology, Weifang People's Hospital, Weifang, 261042, Shandong, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology, Weifang People's Hospital, Weifang, 261042, Shandong, China.
authors.forename: Hongkai
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D004564:Electrocoagulation / Q000009:adverse effects*; D007172:Erectile Dysfunction / Q000209:etiology* / Q000628:therapy*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells; D011468:Prostatectomy / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: Brain-derived neurotrophic factor (BDNF); Electrocautery injury; Erectile dysfunction (ED); Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs); Radical prostatectomy (RP)