Abstract
Erectile dysfunction (ED) is a common complication in men suffered with diabetic mellitus. Stem cell transplantation is a promising strategy for the treatment of diabetic ED (DED). In this study, we evaluated whether combined transplantation of adipose tissue-derived stem cells (ADSCs) and endothelial progenitor cells (EPCs) could improve the erectile function of the DED rat model. DED rats were induced via intraperitoneal injection of streptozotocin (50 mg/kg), and ED was screened by apomorphine (100 mg/kg). DED rats were divided into 4 groups (n = 14 each): DED, ADSC, EPC, and ADSC/EPC group. Another 14 age-matched male SD rats with normal erectile function were served as the normal group. The normal group and the DED group were received intracavernous injection with phosphate-buffered saline (PBS). And the other groups were received intracavernous injection with ADSCs (1 × 106), EPCs (1 × 106), and ADSCs/EPCs (0.5 × 106/0.5 × 106), respectively. The total intracavernous pressure (ICP) and mean arterial pressure (MAP) were recorded at day 28 after injection. The endothelium, smooth muscle, and penile dorsal nerves were assessed within cavernoursal tissue. On day 28 after injection, the ADSC/EPC group displayed more significantly enhanced ICP and ICP/MAP than the DED or ADSC or EPC group (p < 0.05). Immunofluorescent analysis and western blot demonstrated that the improvement of erectile function in the ADSC/EPC5 group was associated with increased expression of endothelial marker (CD31) and the correction of eNOS-cGMP-NO signaling. More 5-ethynyl-2′-deoxyuridine- (EdU-) positive EPCs could be found lining in the cavernous endothelial layer in the ADSC/EPC group than the EPC group, which was attributed to the paracrine of vascular endothelial growth factor (VEGF) and stromal-derived factor-1 (SDF-1) by ADSCs. Combined transplantation of ADSCs and EPCs has a synergic effect in repairing the endothelial function of DED rats, and the underlying mechanism might be the paracrine of VEGF and SDF-1 by ADSCs, which improves the recruitment and proliferation of EPCs in the cavernosum.
Highlights
Erectile dysfunction (ED), which is defined as an inability to obtain and/or sustain sufficient penile erection to achieve satisfactory sexual intercourse, is a common and depressing complication in men suffered with diabetes mellitus [1]
Phosphodiesterase type 5 inhibitors (PDE-5Is) are the first-line treatment for ED nowadays, the response rate in the diabetic ED patients is low [3], mainly because of the severe damaged of cavernousum endothelial function, Stem Cells International subsequently decreasing of smooth muscle content and neuropathy [4]
Studies have demonstrated that the number of endothelial progenitor cells (EPCs) in the peripheral blood of diabetic ED patients was significantly decreased compared to the healthy men, and the function of EPCs was impaired, which indicated that EPCs might be involved in Normal diabetic mellitus erectile dysfunction (DED) adipose tissue-derived stem cells (ADSCs) EPCs ADSCs/EPCs vascular endothelial growth factor (VEGF)
Summary
Erectile dysfunction (ED), which is defined as an inability to obtain and/or sustain sufficient penile erection to achieve satisfactory sexual intercourse, is a common and depressing complication in men suffered with diabetes mellitus [1]. Phosphodiesterase type 5 inhibitors (PDE-5Is) are the first-line treatment for ED nowadays, the response rate in the diabetic ED patients is low [3], mainly because of the severe damaged of cavernousum endothelial function, Stem Cells International subsequently decreasing of smooth muscle content and neuropathy [4]. Stem cells (SCs) are considered one of the promising strategies for diabetic mellitus erectile dysfunction (DED) [5]. ADSCs genetically modified with VEGF-165 displayed a greater therapeutic effect in improving erectile function of DED rats than unmodified ADSCs [8]. Taking into account the risk of the exogenous gene integrating into host genome, transgenic technology is still restricted in clinical application
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