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Updated: Dec 17, 2025
The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
Published on: November 26, 2015
Exosomes derived from mouse inner ear stem cells attenuate gentamicin-induced ototoxicity in vitro through the
Ruosha Lai1, Cuiyun Cai1, Weijing Wu1
1Department of Otolaryngology and Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
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.
Insights
Inner ear stem cell-derived exosomes (IESCs-ex) protect against gentamicin-induced ototoxicity. These exosomes, particularly those enriched with miR-182-5p, reduce oxidative stress and apoptosis in cochlear hair cells.
Area of Science:
- Ototoxicity Research
- Stem Cell Biology
- Exosome Therapeutics
Background:
- Gentamicin causes cochlear hair cell damage via oxidative stress and apoptosis.
- Inner ear stem cells (IESCs) show potential for ototoxicity attenuation.
- The role of IESCs-derived exosomes (IESCs-ex) in this protective effect remains unclear.
Purpose of the Study:
- To investigate if IESCs-ex can protect cochlear hair cells from gentamicin-induced ototoxicity.
- To elucidate the underlying molecular mechanisms, focusing on miR-182-5p and the FOXO3 pathway.
Main Methods:
- Established a gentamicin-induced ototoxicity model using HEI-OC1 cells.
- Treated ototoxic cells with exosomes derived from normal or miR-182-5p-manipulated IESCs.
- Assessed cell viability (MTT assay) and oxidative stress markers (MDA, SOD, CAT, GPx).
- Quantified miR-182-5p, FOXO3, Bcl-2, and Bax expression levels.
Main Results:
- IESCs-ex significantly improved HEI-OC1 cell viability and alleviated gentamicin-induced oxidative stress.
- IESCs-ex treatment led to increased miR-182-5p and decreased FOXO3 expression.
- Exosomes from miR-182-5p-enriched IESCs further enhanced protective effects, modulating apoptosis-related proteins (Bcl-2, Bax).
Conclusions:
- IESCs-ex effectively attenuate gentamicin-induced ototoxicity in cochlear hair cells.
- The protective mechanism involves the miR-182-5p/FOXO3 signaling axis.
- IESCs-ex represent a promising therapeutic strategy for preventing hearing loss caused by ototoxic drugs.
