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Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats

  • Urology - Original Paper
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Abstract

Purpose

Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose-derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabetic rats.

Methods

Forty-five eight-week-old male Sprague–Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabetic rats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured.

Results

We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabetic rats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis.

Conclusions

Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels.

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Acknowledgments

This study was funded by National Natural Science Foundation of China (Nos. 81300478, 81272531), Natural Science Foundation of Jiangsu Province (No. BK20130269), Medical Science Foundation of Jiangsu Province Department of Health (No. H201312), Science and Technology Development Program of Suzhou (No. SYS201450), China Postdoctoral Science Foundation (No. 2015M580466).

Author contributions

Jian-quan Hou, Zhong-cheng Xin, Feng Zhou, and Yu Hui conceived and designed the experiments. Feng Zhou, Yu Hui, Yong-de Xu, Hong-en Lei, Rui-li Guan, and Zhe-zhu Gao performed the experiments. Bi-cheng Yang and Yu Hui were involved in the retrieval and analysis of the data. Yu Hui, Feng Zhou, Jian-quan Hou, and Zhong-cheng Xin participated in the drafting and final editing.

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    Authors and Affiliations

    1. Department of Urology, First Affiliated Hospital of Soochow University, Soochow University, No. 188, Shizi Street, Gusu District, Suzhou, 215006, China

      Feng Zhou, Yu Hui & Jianquan Hou

    2. Molecular Biology Laboratory of Andrology Center, Peking University First Hospital, Peking University, No. A59, Di’anmen West Street, Xicheng District, Beijing, 100034, China

      Yongde Xu, Hongen Lei, Bicheng Yang, Ruili Guan, Zhezhu Gao & Zhongcheng Xin

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    1. Feng Zhou
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    Correspondence to Zhongcheng Xin or Jianquan Hou.

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    The authors declare that they have no conflict of interest.

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    All applicable international, national, and/or institutional guidelines for the care and use of animals were followed, and all procedures performed in studies involving animals were in accordance with the ethical standards of the Committee for Animal Care and Use of Soochow University.

    Additional information

    Feng Zhou, Yu Hui have contributed equally to this work and are considered as co-first authors.

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    Zhou, F., Hui, Y., Xu, Y. et al. Effects of adipose-derived stem cells plus insulin on erectile function in streptozotocin-induced diabetic rats. Int Urol Nephrol 48, 657–669 (2016). https://doi.org/10.1007/s11255-016-1221-3

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    • DOI: https://doi.org/10.1007/s11255-016-1221-3

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