Mammalian inner ears were reported to contain cells that had the ability to proliferate clonally and to differentiate into several types of inner ear cells. Regeneration was reported to occur in vestibules, while the mammalian cochlear cells have been reported to have little ability to regenerate after damage. The inner ear has limited ability to regenerate, while there are other evidences indicating the existence of inner ear stem cells. Potential candidates of stem cells are supporting cells [2], tympanic border cells [3], and other candidates. The total number of them in the inner ear is estimated to be very small, and reported to decrease as the inner ear matures. Tympanic border cells identified as slow-cycling cells have the characteristics of stem cells [3]. Immunohistochemical analysis indicated that these cells stained positive for immature cell marker nestin. The number of slow-cycling cells in the tympanic border cells decreased dramatically in about 2 weeks after birth as the cochlea matured.

ESCs are widely used for the generation of knock-out/knock-in animals, chimeras, and clones. Nowadays, these genetically modified animals are indispensable tools for biological research and animal industry. Extending this study, ESCs were induced to differentiate into a wide variety of cell types including hepatocytes, pancreatic islet cells, blood cells, chondrocytes, cardiomyocytes, dopaminergic neurons, Schwann cells, retinal pigmented epithelium and so on, and expected to be applied in clinics.

iPSCs are somatic-cell-derived stem cells similar to ESCs in terms of self-renewal and pluripotency [4]. iPSCs are similar to mouse ESCs in many points such as an expression of stem cell. The regeneration of the auditory pathway by transplants of fetal brain tissue was first demonstrated [5]. Since then several stem cell-based approaches to cure deafness using mesenchymal stem cells, neural stem cells, ESCs, and iPSCs have been adopted. Current major targets are cochlear hair cells and spiral ganglion neurons (SGNs), which are primarily compromised and unregenerable cells in sensorineural hearing loss. Inner ear hair cells of the mammals have very little capacity of regeneration [6]. This is one major reason for the difficulty in recovering from permanent profound hearing loss. One suggested modality for the recovery from the hearing impairment is the regeneration of hair cells. Hair cell induction from pluripotent stem cells has gradually become a reliable method. Hurdles still exist before the realization of hair cell regeneration. It is still necessary to improve the induction rate, and to develop the method to specifically induce cochlear hair cells. More fundamental difficulty is the in vivo application of induced hair cells. It is not realistic to transplant mature hair cells and to arrange them in the cochlear epithelium [7]. Introduction of stem cells that are programmed to differentiate to inner ear sensory fates and introduction of stem cell-based factor releasing cells may also be other possible strategies.