Cochlear-Bioelectrode: Auditory response to cochlear implant can be improved by stem cell delivery into inner ear in a pig model

Abstract

Cochlear implant (CI) is the most successful auditory prosthesis and has changed the life for nearly half million people with profound hearing loss. The number and function of spiral ganglion neurons (SGNs) in the cochlea are crucial to CI performance. Clinically, some patients with SGNs degeneration fail to return to normal life due to unsatisfactory performance of their CIs. In this study, we show in a swine model that combined stem cell delivery and electrical stimulation (ES) via CI (defined as Cochlear-Bioelectrode) achieved stem cell enrichment near the SGNs and lowered CI stimulation thresholds. ES generated by the cochlear implant electrode array guided human induced pluripotent stem cells (hiPSCs) with a green fluorescent protein (GFP) marker to cross the osseous spiral lamina via naturally existing openings and congregate in the SGN region. In seven days, surprisingly efficient hiPSC migration into the SGN region was demonstrated, while hiPSC delivery and enrichment in the SGN region failed without ES. After two weeks of combined electric stimulation and stem cell delivery treatment, the number of SGNs increased significantly in the 60-day old pig model (mean number = 129.6/field), as compared to untreated deafness pigs of the same age (mean number = 6.2/field). With the replenished SGNs, CI stimulation thresholds were significantly reduced and hearing sensitivity and dynamic range extended, as demonstrated by electrically evoked auditory brainstem responses. Our findings provide the first evidence that in vivo Cochlear-Bioelectrode (CBe) may be feasible with broad promising clinical applications.