Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats

Yan Zhang; Jun Yang; Li Zhuan; Guanghui Zang; Tao Wang; Jihong Liu

doi:10.7717/peerj.7507

Transplantation of adipose-derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus-induced erectile dysfunction in rats

PeerJ. 2019 Aug 12:7:e7507. doi: 10.7717/peerj.7507. eCollection 2019.

Authors

Yan Zhang^{1

2}, Jun Yang^{1

2}, Li Zhuan³, Guanghui Zang⁴, Tao Wang^{1

2}, Jihong Liu^{1

2}

Affiliations

¹ Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
² Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³ Department of Reproductive Medicine, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
⁴ Department of Urology, Xuzhou Central Hospital, Xuzhou, Jiangsu, China.

Abstract

Background: Erectile dysfunction is a major complication of diabetes mellitus. Adipose-derived stem cells (ADSCs) have attracted much attention as a promising tool for the treatment of diabetes mellitus-induced erectile dysfunction (DMED). Inducible nitric oxide synthase (iNOS) plays an important role in protecting penile tissues from fibrosis. The aim of this study was to determine the efficacy of ADSCs overexpressing iNOS on DMED in rats.

Methods: ADSCs were isolated and infected with adenovirus overexpressing iNOS (named as ADSCs-iNOS). The expression of iNOS was detected using western blot analysis and real-time PCR. Rats were randomly assigned into five groups: control group, DMED group, ADSCs group, ADSCs-EGFP group and ADSCs-iNOS group. 5 × 10⁵ cells were given once via the intracorporal route. Two weeks after treatment, erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were obtained and evaluated at histology level.

Results: We found that ADSCs-iNOS had significantly higher expression of iNOS at mRNA and protein levels and generated more nitric oxide (NO). ADSCs-iNOS reduced collagen I and collagen IV expression of corpus cavernosum smooth muscle cells (CCSMCs) in cell co-culture model. Transforming growth factor-β1 expression in CCSMCs reduced following co-culture with ADSCs-iNOS. Injection of ADSCs-iNOS significantly ameliorated DMED in rats and decreased collagen/smooth muscle cell ratio of penile tissues. Moreover, elevated NO and cyclic guanosine monophosphate concentrations were detected in penile tissues of ADSCs-iNOS group.

Conclusion: Taken together, ADSCs-iNOS significantly improved erectile function of DMED rats. The therapeutic effect may be achieved by increased NO generation and the suppression of collagen I and collagen IV expression in the CCSMCs to decrease penile fibrosis.

Keywords: Diabetes mellitus; Erectile dysfunction; Inducible nitric oxide synthase; Stem cells.

Grants and funding

The work was funded by the National Natural Science Foundation of China (grant no. 81070484). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.