Cell- and gene-therapy approaches to inner ear repair

Sensorineural hearing loss is the most common sensory disorder in humans. It is primarily due to the degeneration of highly specialised mechanosensory cells in the cochlea, the so-called hair cells. Hearing problems can also be caused or further aggravated by the death of auditory sensory neurons that convey the information from the hair cells to the brain stem. Despite the discovery of stem/progenitor cells in the mammalian cochlea, no regeneration of either damaged hair cells or auditory neurons has been observed in mammals, in contrast to what is seen in avians and non-mammalian vertebrates. The reasons for this divergence have not yet been elucidated, although loss of stem cells and/or loss of their phenotypic plasticity in adult mammals have been put forward as possible explanations. Given the high incidence of this disorder and its economic and social implications, a considerable number of research lines have been set up aimed towards the regeneration of cochlear sensory cell types. This review summarizes the various routes that have been explored, ranging from the genetic modification of endogenous cells remaining in the inner ear in order to promote their transdifferentiation, to the implantation of exogenous stem or progenitor cells and their subsequent differentiation within the host tissue. Prophylactic treatments to fight against progressive sensory cell degeneration in the inner ear are also discussed.