The effect of a single intracavernous injection of autologous adipose-derived stem cells in patients with erectile dysfunction following radical cystectomy

Abstract Background：Diabetes mellitus (DM) is an important risk factor for erectile dysfunction (ED). Adipose-derived stem cells (ADSCs) and low-intensity extracorporeal shockwave therapy (LI-ESWT) are two emerging therapies for ED. The efficacy of ADSCs combined LI-ESWT in the treatment of diabetes induced erectile dysfunction (DMED) was not completely elucidated. This study aim to investigate combined therapeutic efficacy of ADSCs and LI-ESWT in rat model of DMEDand whether they have interaction.Methods：Rats were randomly divided into 5 groups: control, erectile dysfunction group (ED), ADSCs treatment group(ADSCs), LI-ESWT treatment group (LI-ESWT) and ADSCs combined with LI-ESWT treatment (ADSCs+LI-ESWT). After 4 weeks, erectile function was assessed using intracavernous pressure (ICP) and mean arterial pressure (MAP), after that performed immunohistochemistry (IH).Results：Finally, a total of 98 rats completed the experiment. The ICP/MAP of five groups under the voltage stimulation of 10V was significantly different (P>0.05). ICP/MAP in ADSC group, LI-ESWT group and combined treatment group was significantly higher than that of ED model group; ICP/MAP in combined treatment group was higher than ADSC group and LI-ESWT group. Interaction between LI-ESWT and ADSCs therapy was not statistically significant (P＞0.05).The expression of -smooth muscle actin (-SMA), nerve nitricoxide synthase (nNOS) and von Willebrand factor (vWF) in ADSCs treatment group, LI-ESWT group and combined treatment group was higher than those in ED model group (P < 0.05).Conclusions：Both ADSCs and LI-ESWT therapy can improve the erectile function of rats. The combination of these two methods present better effect on ED than used individually. There is no positive interaction between ADSCs therapy and LI-ESWT. Both ADSCs and LI-ESWT can enhance the expression of α-SMA, nNOS and vWF in corpus cavernosum of ED rats.

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

10.7287/peerj.preprints.27737v1 ◽

2019 ◽

Author(s):

Yan Zhang ◽

Jun Yang ◽

Li Zhuan ◽

Guanghui Zang ◽

Tao Wang ◽

...

Keyword(s):

Nitric Oxide ◽

Diabetes Mellitus ◽

Stem Cells ◽

Smooth Muscle ◽

Erectile Dysfunction ◽

Inducible Nitric Oxide Synthase ◽

Collagen Iv ◽

Adipose Derived Stem Cells ◽

Oxide Synthase ◽

Inducible Nitric Oxide

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.

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