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Beneficial effect of PEDF-transfected ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model

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Abstract

Diabetes mellitus (DM) is an important risk factor for erectile dysfunction. Adipose-derived stem cells (ADSCs) are essential for maintaining erectile function but their function is impaired during hyperglycemia. To evaluate the effects of pigment epithelium-derived factor (PEDF)-transfected ADSCs on the restoration of erectile function ADSCs and PEDF-transfected ADSCs were exposed to normal or high glucose levels for 72 h and the effects on cell survival and protein expression were determined. For in vivo studies, rats with streptozocin-induced DM were intravenously injected with ADSCs or PEDF-transfected ADSCs. Two weeks later, the intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured to assess erectile function, and penile tissues were harvested for further evaluation. PEDF overexpression in ADSCs protected cells against hyperglycemia-induced apoptosis (as determined by a TUNEL assay), increasing the expression of neurotrophic factors and decreasing the expression of inflammatory cytokines and oxidative stress-related proteins (as determined by western blotting and ELISA). In DM rats, transplantation with PEDF-transfected ADSCs effectively restored erectile function, as determined by the ICP/MAP ratio, compared with untreated ADSCs. PEDF overexpression also resulted in higher survival rates and decreased apoptosis of ADSCs. Promotion of neurotrophic factor expression and suppression of inflammatory cytokines and oxidative stress-related proteins were also observed after transplantation of PEDF-transfected ADSCs. Thus, our results demonstrate that transplantation of ADSCs restored erectile function in a rat model of DM, attenuating the negative effects of hyperglycemia. These findings indicate the therapeutic potential of ADSCs for treating erectile dysfunction and the additional benefits of PEDF overexpression.

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Acknowledgment

This work was supported by the National Science Foundation for Young Scientists of China (Grant No. 81200504 and 81400755).

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    Authors and Affiliations

    1. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, No. 100, Haining Road, Hongkou District, Shanghai, 200080, China

      Jun Lu, Zhixiang Xin, Qi Zhang, Di Cui, Yinglong Xiao, Jian Zhuo, Feng Sun, Shujie Xia & Yi Shao

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    1. Jun Lu
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    2. Zhixiang Xin
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    3. Qi Zhang
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    Correspondence to Shujie Xia or Yi Shao.

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    Jun Lu and Zhixiang Xin are co-first authors.

    Jun Lu and Zhixiang Xin contributed equally to this work.

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    Lu, J., Xin, Z., Zhang, Q. et al. Beneficial effect of PEDF-transfected ADSCs on erectile dysfunction in a streptozotocin-diabetic rat model. Cell Tissue Res 366, 623–637 (2016). https://doi.org/10.1007/s00441-016-2494-7

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