Advances in Stem Cell Therapy for Hearing Loss

Hearing loss is the most common sensory disorder, causing substantial impacts on language development, literacy, mood, and cognition. Sensorineural hearing loss, caused by injury to the cochlear hair cells, cochlear nerve, or central auditory pathways, accounts for most cases of hearing loss. Existing therapies for sensorineural hearing loss include hearing aids and cochlear implants; however, these modalities have limited efficacy in noisy environments, variable hearing outcomes, and limited frequency discrimination. There are currently no Food and Drug Administration-approved cellular, molecular, or pharmacological therapies available. Stem cell therapy is an emerging and promising approach to treating sensorineural hearing loss through transplanting exogenous stem cells into the cochlea. Stem cell-based inner ear systems have been crucial to studying how stem cells can mimic or restore the function of the inner ear. The two-dimensional culture system has been instrumental in understanding pluripotent stem cell differentiation in the inner ear neuroepithelium. However, they are unable to mimic tissue-specific architecture and specific cellular interactions. Researchers subsequently moved to develop differentiation protocols in three-dimensional inner ear organoids, which more closely resemble in vivo structures. Such approaches are a promising step forward in the development of stem cell therapies focusing on structures in the cochlea that have limited to no ability to regenerate, including hair cells, spiral ganglion neurons, and spiral ligament fibrocytes. Future directions of this field include integrating stem cell therapy with gene therapy approaches and developing novel high-throughput drug screening platforms.