Transplantation of adipose derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus induced erectile dysfunction in rats
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Abstract
Background: Erectile dysfunction is a major complication of diabetes mellitus. Adipose derived stem cells (ADSCs) has 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. 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 and p-Smad2/3 to Smad2/3 ratio 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 nitric oxide and cGMP concentrations were detected in penile tissues of ADSCs-iNOS group.
Conclusion: Taken together, ADSCs-iNOS significantly improve erectile function of DMED rats. The therapeutic effect may be achieved by increased nitric oxide generation and the suppression of collagen I and collagen IV expression in the CCSMCs to decrease penile fibrosis.
Cite this as
2019. Transplantation of adipose derived stem cells overexpressing inducible nitric oxide synthase ameliorates diabetes mellitus induced erectile dysfunction in rats. PeerJ Preprints 7:e27737v1 https://doi.org/10.7287/peerj.preprints.27737v1note This preprint is not peer-reviewed. You may wish to reference the subsequent peer-reviewed version of this article.
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Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Yan Zhang performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Jun Yang performed the experiments, contributed reagents/materials/analysis tools, authored or reviewed drafts of the paper, approved the final draft.
Li Zhuan performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, prepared figures and/or tables, approved the final draft.
Guanghui Zang performed the experiments, contributed reagents/materials/analysis tools, approved the final draft.
Tao Wang conceived and designed the experiments, approved the final draft.
Jihong Liu conceived and designed the experiments, approved the final draft.
Animal Ethics
The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers):
Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology approved animal experiments of this study (TJ-A20131213)
Data Deposition
The following information was supplied regarding data availability:
The raw measurements are provided in the supplementary file.
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.
