Novel insights into inner ear development and regeneration for targeted hearing loss therapies.

Sensorineural hearing loss is the most common sensory deficit in humans. Despite the global scale of the problem, only limited treatment options are available today. The mammalian inner ear is a highly specialized postmitotic organ, which lacks proliferative or regenerative capacity. Since the discovery of hair cell regeneration in non-mammalian species however, much attention has been placed on identifying possible strategies to reactivate similar responses in humans. The development of successful regenerative approaches for hearing loss strongly depends on a detailed understanding of the mechanisms that control human inner ear cellular specification, differentiation and function, as well as on the development of robust in vitro cellular assays, based on human inner ear cells, to study these processes and optimize therapeutic interventions. We summarize here some aspects of inner ear development and strategies to induce regeneration that have been investigated in rodents. Moreover, we discuss recent findings in human inner ear development and compare the results with findings from animal models. Finally, we provide an overview of strategies for in vitro generation of human sensory cells from pluripotent and somatic progenitors that may provide a platform for drug development and validation of therapeutic strategies in vitro.

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