Potential therapeutic effect of stem cells on sensorineural hearing loss

Sensorineural hearing loss (SNHL) remains a global health challenge with limited regenerative therapeutic options. This review delineates advancements in stem cell-based therapies, emphasizing their potential to restore auditory function through cellular regeneration and molecular modulation. Stem cells, including mesenchymal (MSCs), induced pluripotent (iPSCs), and embryonic stem cells (ESCs), exhibit multilineage differentiation and paracrine signaling capabilities, enabling hair cell (HC) regeneration, spiral ganglion neuron (SGN) repair, and inflammation modulation. Cochlear organoid models derived from stem cells have advanced mechanistic studies, though challenges persist in replicating cochlear-specific HC phenotypes. Exosomes, as nanoscale bioactive vesicles, demonstrate enhanced biocompatibility and barrier penetration, effectively mitigating oxidative stress, apoptosis, and aminoglycoside ototoxicity while promoting HC survival. Gene-editing technologies, notably CRISPR-Cas9 and adeno-associated virus (AAV) gene delivery system, synergize with stem cell platforms to correct pathogenic mutations and engineer therapeutic cells for targeted inner ear repair. Preclinical studies highlight MSC transplantation and exosome administration in improving auditory thresholds and neuronal morphology, yet clinical translation faces hurdles including delivery precision, immune responses, and scalability. Current limitations in replicating cochlear cytoarchitecture and standardizing differentiation protocols necessitate further exploration of combinatorial strategies, such as integrating stem cell therapy with cochlear implants or medicaments delivery systems. Future research need prioritize optimizing cell lineage specification, enhancing exosome targeting, and validating long-term safety to realize the transformative potential of regenerative medicine in SNHL treatment.