Exosomes derived from mouse inner ear stem cells attenuate gentamicin‐induced ototoxicity in vitro through the miR‐182‐5p/FOXO3 axis

Gentamicin-induced cochlear hair cell ototoxicity, such as oxidative stress and apoptosis, could be attenuated by mouse inner ear stem cells (IESCs). However, it is still unclear whether such protective effects could be mediated by exosomes derived from IESCs (IESCs-ex). In the present study, HEI-OC1 cells were exposed to gentamicin (2 mM) to establish an ototoxicity model and further treated with exosomes isolated from miR-182-5p transferred or non-transferred IESCs. IESCs-ex improved HEI-OC1 cell viability, as assayed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide method, and alleviated the oxidative stress response induced by the gentamicin treatment, as confirmed by measuring the malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase levels. IESCs-ex increased relative miR-182-5p expression and decreased FOXO3 expression in the gentamicin-exposed HEI-OC1 cells. Furthermore, exosomes derived from miR-182-5p mimics that were pre-treated with IESCs could increase miR-182-5p and Bcl-2 expressions and decrease FOXO3 and Bax expressions in gentamicin-exposed HEI-OC1 cells. All of these results indicate that IESCs-ex could attenuate gentamicin-induced HEI-OC1 cell apoptosis and oxidative stress through the miR-182-5p/FOXO3 axis.