Mesenchymal vs. induced pluripotent stem cells: potential for spiral ganglion neuron regeneration in auditory neuropathy

Auditory neuropathy is a distinct form of sensorineural hearing loss characterized by dysfunction or degeneration of primary auditory neurons, also known as spiral ganglion neurons (SGNs), which transmit acoustic information from the cochlea to the brain. Increasing evidence indicates that SGNs are particularly susceptible to degeneration induced by noise exposure, ototoxic agents, genetic mutations, or aging, often preceding the loss of cochlear mechanosensory hair cells, and thus represents a critical target for regenerative intervention for auditory neuropathy. Stem cell-based approaches have emerged as promising strategies to restore auditory nerve function. In particular, the generation of otic neuronal progenitors (ONPs) capable of replacing damaged SGNs offers a translationally relevant avenue for therapy. Among candidate sources, mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) offer distinct biological and translational advantages. iPSCs provide robust pluripotency and developmental recapitulation capacity, enabling efficient differentiation toward otic neuronal lineages, whereas MSCs offer immunomodulatory properties and paracrine neurotrophic support with lower tumorigenic risk. This mini-review critically compares MSC and iPSC-derived ONPs in terms of differentiation efficiency, neuronal maturation, integration potential, immunogenicity, and scalability. We further discuss emerging complementary strategies, including ONP transplantation, glial cell reprogramming and extracellular vesicle-based therapies. Together, these approaches highlight converging regenerative paradigms aimed at restoring auditory neuron function in neuropathic hearing loss.