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BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury

  • Urology - Original Paper
  • Published:
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Abstract

Purpose

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.

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Acknowledgments

This study was funded by the National Natural Science Foundation of China (30901489); Scientific Research Foundation for Returned Scholars Ministry of Education of China; Shanghai Jiaotong University Biomedical Engineering cross research foundation (YG2014MS15); Shandong science and technology development plan (2011GGH21813).

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    Authors and Affiliations

    1. Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

      Lujie Song, Zhiqiang Cui, Qiang Fu & Jianwen Huang

    2. Department of Urology, the Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 300211, China

      Jianqiang Zhu

    3. Department of Burn and Plastic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, 197 Ruijin Second Road, Shanghai, 200025, China

      Xiong Zhang

    4. Department of Urology, Weifang People’s Hospital, Weifang, 261042, Shandong, China

      Zhiqiang Cui & Hongkai Lu

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    1. Lujie Song
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    Correspondence to Xiong Zhang.

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    Lujie Song and Jianqiang Zhu have contributed equally to this work and are considered as co-first authors.

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    Song, L., Zhu, J., Zhang, X. et al. BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury. Int Urol Nephrol 48, 37–45 (2016). https://doi.org/10.1007/s11255-015-1154-2

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