Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models

Stem Cell Res Ther. 2021 Jan 25;12(1):87. doi: 10.1186/s13287-021-02161-8.

Abstract

Background: Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED.

Methods: In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs).

Results: Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p.

Conclusions: Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA.

Keywords: Autophagy; Chronic intermittent hypoxia; Erectile dysfunction; Exosomes; miR-301a-3p.