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

Background: The cochlear implant (CI) is the most successful neural prosthesis and has improved the quality of life for over one million people with profound hearing loss. The number and function of spiral ganglion neurons (SGNs) in the cochlea are crucial to CI performance. Clinically, patients with significant SGN degeneration fail to return to normal life due to unsatisfactory performance of their CIs. This study aims to explore the efficacy of improve auditory function by delivering stem cells into the SGN region using a customized CI (defined as Cochlear-Bioelectrode). Methods: Human induced pluripotent stem cells (hiPSCs) with a green fluorescent protein (GFP) marker were delivered cross the osseous spiral lamina via naturally existing openings and congregate in the SGN region by Cochlear-Bioelectrode after Cochlear implantation, electrically evoked auditory brainstem responses (EABR) were compared between those with and without stem cells delivery. Results: In seven days, efficient hiPSC migration into the SGN region was demonstrated with concurrent electric stimulation and stem cell delivery, while hipsc did not migrate into the sgn region with stem cell delivery alone. 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 ± 1.61/field), compared to untreated deafness pigs of the same age (mean number = 6.2 ± 0.92/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. Conclusions: Our results showed that in vivo concurrent cochlear implant stimulation and hipsc delivery increased stem cells in the sgn region and lowered ci stimulation thresholds, paving the way to broad and promising clinical applications.