Intratympanic injection of MSC-derived small extracellular vesicles protects spiral ganglion neurons from degeneration
Anning Chen, Jiaxi Qu, Yunyou You, Jing Pan, Verena Scheper, Yongdong Lin, Xuexin Tian, Fan Shu, Yanjing Luo, Jie Tang, Hongzheng Zhang
Abstract
Sensorineural hearing loss is one of the most prevalent sensory deficits. Spiral ganglion neurons (SGNs) exhibit very limited regeneration capacity and their degeneration leads to profound hearing loss. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEV) have been demonstrated to repair tissue damage in various degenerative diseases. However, the effects of MSC-sEV on SGN degeneration remain unclear. In this study, we investigated the efficacy of MSC-sEV for protection against ouabain-induced SGN degeneration. MSC-sEV were derived from rat bone marrow and their components related to neuron growth were determined by proteomic analysis. In primary culture SGNs, MSC-sEV significantly promoted neurite growth and growth cone development. The RNA-Seq analysis of SGNs showed that enriched pathways include neuron development and axon regeneration, consistent with proteomics. In ouabain induced SGN degeneration rat model, MSC-sEV administration via intratympanic injection significantly enhanced SGN survival and mitigated hearing loss. Furthermore, after ouabain treatment, SGNs displayed evident signs of apoptosis, including nuclei condensation and fragmentation, with numerous cells exhibiting TUNEL-positive. However, administration of MSC-sEV effectively decreased the number of TUNEL-positive cells and reduced caspase-3 activation. In conclusion, our findings demonstrate the potential of MSC-sEV in preventing SGN degeneration and promoting neural growth, suggesting intratympanic injection of MSC-sEV is a specific and efficient strategy for neural hearing loss. • MSC-sEV were employed for the first time in treating SGN degeneration, demonstrating outstanding protective and repair efficacy. • Proteomics and RNA-seq were combined to unveil the potential mechanisms by which MSC-sEV promote SGN growth. • Intratympanic injection of MSC-sEV minimizes surgical trauma and systemic side effects, showing promise for future clinical use.