MSC-derived exosomes ameliorate erectile dysfunction by alleviation of corpus cavernosum smooth muscle apoptosis in a rat model of cavernous nerve injury

BACKGROUND: This study investigated the therapeutic effects of MSC-derived exosomes (MSC-Exos) on erectile function in a rat model of cavernous nerve injury (CNI). METHODS: MSCs were isolated from rat bone marrow and exosomes were isolated from the supernatants by ultracentrifugation. The tissue explant adherent method was used to isolate and culture corpus cavernosum smooth muscle cells (CCSMCs). MSCs and CCSMCs were identified by flow cytometry, in vitro differentiation or immunofluorescence staining. Thirty-two 10-week-old male Sprague Dawley (SD) rats were divided into four groups: a sham operation group and bilateral CNI groups that received intracavernosal (IC) injection of either PBS, MSCs or MSC-Exos. Four weeks after CNI and treatment, the erectile function of the rats was measured by electrically stimulating the cavernous nerve. The penile tissues were harvested for blinded histologic analysis and western blotting. H(2)O(2) was used to induce apoptosis in the CCSMCs, and a flow cytometer was used to measure the cell viability of the CCSMCs treated with or without exosomes in vitro. RESULTS: Recovery of erectile function was observed in the MSC-Exos group. The MSC-Exos treatment significantly enhanced smooth muscle content and neuronal nitric oxide synthase in the corpus cavernosum. The ratio of smooth muscle to collagen in the corpus cavernosum was significantly improved in the MSC-Exos treatment group compared to the PBS vehicle group. WB confirmed these biological changes. Cell viability of the CCSMCs was increased in the MSC-Exos-treated groups, and caspase-3 expression was decreased after the MSC-Exos treatment in vivo and in vitro. CONCLUSIONS: Exosomes isolated from MSCs culture supernatants by ultracentrifugation could ameliorate CNI-induced ED in rats by inhibiting apoptosis in CCSMCs, with similar potency to that observed in the MSCs-treated group. Therefore, this cell-free therapy has great potential for application in the treatment of CNI-induced ED for replacing cell therapy. GRAPHICAL ABSTRACT: MSC-derived exosomes ameliorate erectile dysfunction in a rat model of cavernous nerve injury [Image: see text]