Adipose-Derived Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes

Abstract Background The efficacy of adipose-derived stem cells (ADSCs) in alleviating erectile dysfunction (ED) of diabetic rats has been demonstrated mainly through a paracrine effect. However, exosomes (EXOs), which are important bioactive substance vectors secreted by ADSCs, have never been associated with ED. Aim To investigate the effect of ADSC-derived EXOs on erectile function in a type 2 diabetic ED rat model. Methods EXOs were isolated from the supernatants of cultured ADSCs by ultracentrifugation. We constructed a type 2 diabetic rat model using a high-fat diet and low-dose streptozotocin administered by intraperitoneal injection. In total, 24 diabetic rats were randomly assigned to three groups and were treated with an intracavernous injection of ADSC-derived EXOs, ADSCs, or phosphate buffered saline. Another eight age-matched rats underwent sham operation and composed the normal control group. Outcomes Intracavernous pressure and mean arterial pressure testing and histologic and western blot analyses were performed 4 weeks after the intracavernous injection. Results ADSC-derived EXOs and ADSCs administered by intracavernous injection led to an increase in the ratio of intracavernous pressure to mean arterial pressure compared with that for phosphate buffered saline treatment. Histologic and western blot analyses demonstrated an increased ratio of smooth muscle to collagen, increased expression of an endothelial marker (CD31), a smooth muscle marker (α-smooth muscle actin), and antiapoptotic protein Bcl-2 and decreased the expression of the apoptotic protein cleaved caspase-3 and apoptosis of endothelial and smooth muscle cells in the corpus cavernosum tissue after EXO or ADSC injection compared with values for the phosphate buffered saline treatment. Clinical Translation The present results are expected to provide a scientific foundation for clinical application in the near future. Strengths and Limitations Although the results demonstrated that intracavernous injection of ADSC-derived EXOs could ameliorate ED of diabetic rats, the optimum dose and times of injection remain for further study. Conclusions ADSC-derived EXOs, similarly to ADSCs, were capable of rescuing corpus cavernosum endothelial and smooth muscle cells by inhibiting apoptosis and thus promoting the recovery of erectile function in type 2 diabetic rats.