Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies

Abstract

ABSTRACT The sensory epithelia of the mammalian inner ear enable sound and movement to be perceived. Damage to these epithelia can cause irreversible sensorineural hearing loss and vestibular dysfunction because they lack regenerative capacity. The human inner ear cannot be biopsied without causing permanent damage, significantly limiting the tissue samples available for research. Investigating disease pathology and therapeutic developments have therefore traditionally relied on animal models, which often cannot completely recapitulate the human otic systems. These challenges are now being partly addressed using induced pluripotent stem cell-derived cultures, which generate the sensory epithelial-like tissues of the inner ear. Here, we review how pluripotent stem cells have been used to produce two-dimensional and three-dimensional otic cultures, the strengths and limitations of these new approaches, and how they have been employed to investigate genetic and acquired forms of audiovestibular dysfunction. This Review provides an overview of the progress in pluripotent stem cell-derived otic cultures thus far, focusing on their applications in disease modelling and therapeutic trials. We survey their current limitations and future directions, highlighting their prospective utility for high-throughput drug screening and developing personalised medicine approaches.