MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

Abstract

AbstractIncreasing incidence of sensorineural hearing loss (SNHL) has raised concerns over the disease, while the limited treatment options have motivated the study of new biological therapies. Among these, mesenchymal stem cell (MSC) transplantation has been shown to improve hearing function, and accumulating evidence indicates that MSCs could impart their therapeutic effects by secreting exosomes. However, the underlying therapeutic mechanisms are not fully understood. Herein, in a neomycin-induced SNHL model, we found that exosomes released by MSCs rescued hearing loss and ameliorated hair cell loss by regulating autophagy of the recipient hair cells. Mechanistically, exogenous exosomes could be engulfed by hair cells after treatment. Then, in the hair cells, exosomes promoted the expression of endocytic genes and the formation of endosomes, thus inducing autophagy activation. Finally, the enhanced autophagy promoted cell survival, reduced mitochondrial oxidative stress and apoptosis of hair cells, and attenuated neomycin-induced ototoxic damage. Collectively, our study unveiled the otoprotective role of autophagy activated by exogenous exosomes in hair cells, and verified the potential of extracellular vesicle-based biological therapy for SNHL caused by neomycin.