Exosomes derived from cochlear spiral ganglion progenitor cells prevent cochlea damage from ischemia-reperfusion injury via inhibiting the inflammatory process

Abstract

Ischemia-reperfusion injury (I/R)-induced inflammatory process can mediate cochlea damage-related hearing loss; whether cochlear spiral ganglion progenitor cell-derived exosomes (CSGPC-exos) play a protective role by carrying functional microRNAs into recipient cells is unknown. Different doses of CSGPC-exos (0.1 μg/μl, 0.2 μg/μl, 0.5 μg/μl, 1.0 μg/μl) were administrated into the cochleae of the I/R group induced with 30-min occlusion of the bilateral vertebral arteries and sham surgery group. The speech-evoked auditory brainstem response (ABR) test was utilized to estimate the auditory threshold shift. The relative expression of proinflammatory cytokines was detected with RT-PCR and Western blot, while parvalbumin and caspase-3 expression were detected by immunofluorescence staining in the cochleae. The relative expression of microRNAs (miR-21-5p, miR-26a-5p, and miR-181a-5p) was detected in the cochleae. I/R significantly up-regulated ABR threshold shift and promoted hair cell apoptosis indicated by parvalbumin and caspase-3 staining, while CSGPC-exos (0.5 μg/μl, 1.0 μg/μl) could diminish such damages with downregulated proinflammatory factors (IL-6, IL-1β, TNF-α, and Cox-2) and upregulated anti-inflammatory miRNAs (miR-21-5p, miR-26a-5p, and miR-181a-5p) expression in the cochleae. CSGPC-exos could protect cochleae damage from I/R, probably via inhibiting the inflammatory process.

Keywords: Cochlear spiral ganglion progenitor cells; Exosome; Ischemia-reperfusion injury; MiR-181a-5p; MiR-21-5p; MiR-26a-5p.