Regeneration of sensory hair cells in mature mammals

Hearing loss and balance dysfunction are commonly caused by the loss of sensory hair cells, the cells which detect sound waves in the auditory organs and head movements in the vestibule. Replacement and regeneration of damaged hair cells occurs naturally in non-mammalian vertebrates such as birds and fish. While a small amount of hair cell regeneration occurs in the vestibular organs of mammals even at adult ages, this process only happens in the cochlea during the first days after birth and does not, in either system, result in recovery of function. Here, we review what is known about the natural capacity for hair cell regeneration in mammals, comparing auditory and vestibular organs. We also discuss strategies to induce the formation of new hair cells in the adult inner ear such as reprogramming the remaining supporting cells with genes to drive a hair cell fate or induce proliferation. Finally, we present a roadmap for what is needed to restore auditory and vestibular function and discuss the challenges that remain.