Partial hearing recovery after cochlear nerve surface transplantation of hair follicle‐derived neural crest stem cells in neural hearing loss rat

BACKGROUND: Stem cell therapy offers promise for the neurodegenerative diseases and has been explored for sensorineural hearing loss (SNHL). However, effective cell delivery strategies remain a critical challenge for SNHL treatment. METHODS: To address this need, we established an ouabain-induced SGN injured hearing loss model in rat and evaluated a novel transplantation strategy targeting the cochlear nerve surface via posterior occipital approach, designed to minimize cochlear structural damage and facilitate targeted cell delivery to Rosenthal's canal (RC). The temporal changes in glial cell densities within RC revealed a progressively deteriorating neural microenvironment, supporting early-stage intervention. Accordingly, hair follicle-derived neural crest stem cell (HFNCSC) transplantation was performed 3 or 4 days after modeling via two approaches: cochlear nerve surface transplantation (CNT) and round window transplantation (RWT). RESULTS: CNT resulted in significant improvements in auditory function, as evidenced by reduced auditory brainstem response (ABR) thresholds, shortened wave I latencies, and preserved wave I amplitudes post-transplantation. Transplanted cells were distributed along the nerve trunk and within RC. In contrast, RWT failed to improve auditory function and caused cochlear structural damage, with widespread cell dispersion in cochlear fluids. Notably, the CNT group exhibited significantly higher densities of TUJ1-positive neuron-like cells and glial cells in the RC, accompanied by enhanced myelin basic protein expression suggestive of remyelination. No such improvements were observed in the RWT group. CONCLUSIONS: These findings suggest that cochlear nerve surface transplantation enhances stem cell survival and auditory function recovery, and represents a promising delivery approach for stem cell-based therapy of SGN-related hearing loss.