1. Intratympanic injection of MSC-derived small extracellular vesicles protects spiral ganglion neurons from degeneration.
- Author
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Chen A, Qu J, You Y, Pan J, Scheper V, Lin Y, Tian X, Shu F, Luo Y, Tang J, and Zhang H
- Subjects
- Animals, Rats, Male, Apoptosis drug effects, Neurons drug effects, Neurons pathology, Neurons metabolism, Nerve Degeneration pathology, Cells, Cultured, Disease Models, Animal, Hearing Loss, Sensorineural pathology, Spiral Ganglion drug effects, Spiral Ganglion pathology, Extracellular Vesicles metabolism, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells drug effects, Rats, Sprague-Dawley, Ouabain pharmacology, Injection, Intratympanic
- 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)
- Published
- 2024
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