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

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.

Stem cell therapy and diabetic erectile dysfunction: A critical review

“…Further, the type of stem cells used was autologous and allogenic, and the average number of stem cells injected per animal was 1 × 10 6 cells, which were delivered intra-cavernosally. However, the number of cells injected among these studies ranged from 2 × 10 6 to 5 × 10 5 cells per animal[ 46 , 47 ]. Moreover, in addition to stem cell therapy, several studies added growth factors, hormones and drugs, including insulin[ 48 ], magnetic iron oxide nanoparticles[ 49 ], microtissue[ 50 ], inducible NOS[ 47 ], myocardin[ 51 ], icariin[ 52 ], corin[ 53 ], exosomes from corpus cavernosum smooth muscle cells[ 54 ], fibroblast growth factor 2 (FGF2)[ 55 ], stromal cell-derived cell factor-1 (SDF-1)[ 56 ], VEGF[ 57 ] and hepatocyte growth factor[ 45 ].…”

Couplet medicines of leech and centipede granules improve erectile dysfunction via inactivation of the CaSR/PLC/PKC signaling in streptozotocin-induced diabetic rats

“…As is known, oxidative stress is well recognized as a major pathogenic factor in the pathogenesis of DMED, which characterized by overproduction of ROS [33] and induces endothelial cell injury with the reduction of NO [34]. Numerous reports have indicated that NO plays a crucial role in the induction and maintenance of normal vascular physiology, is released from noncholinergic nerves and endothelium [16,35], and has been clarified that its bioavailability is decreased in the penis of human DMED patients [10,36]. The erectile response and maintain erection relies on the production of NO via nNOS initiates and eNOS, respectively.…”

Human umbilical cord mesenchymal stem cells ameliorate erectile dysfunction in rats with diabetes mellitus through the attenuation of ferroptosis

“…The isolated stem cells showed typical broblast morphology when they were passed to the third CCSMCs were isolated from rat penis, as in our prior investigation [20]. The cells were then identi ed by immuno uorescence staining (Figure .…”

“…The capacity to develop into adipocytes and osteoblasts was then assessed using Oil red O and Alizarin red S staining. Our team's typical approach involved isolating corpus cavernosum smooth muscle cells (CCSMCs) from rat penis and purifying them using a differential adhesion method over the course of two weeks [20]. The CCSMCs were then grown in DMEM with 10% FBS added.…”