Direct cellular reprogramming and inner ear regeneration

Abstract

Introduction: Sound is integral to communication and connects us to the world through speech and music. Cochlear hair cells are essential for converting sounds into neural impulses. However, these cells are highly susceptible to damage from an array of factors, resulting in degeneration and ultimately irreversible hearing loss in humans. Since the discovery of hair cell regeneration in birds, there have been tremendous efforts to identify therapies that could promote hair cell regeneration in mammals.

Areas covered: Here, we will review recent studies describing spontaneous hair cell regeneration and direct cellular reprograming as well as other factors that mediate mammalian hair cell regeneration.

Expert opinion: Numerous combinatorial approaches have successfully reprogrammed non-sensory supporting cells to form hair cells, albeit with limited efficacy and maturation. Studies on epigenetic regulation and transcriptional network of hair cell progenitors may accelerate discovery of more promising reprogramming regimens.

Keywords: Cochlea; hair cell; hearing loss; supporting cell; utricle.

Figure 1.

The organ of Corti, the sensory domain of the cochlea, houses one row of inner hair cells and three rows of outer hair cells. Inner hair cells are supported by inner phalangeal cells and outer hair cells are supported by Deiters’ cells, collectively referred to as supporting cells. The inner and outer hair cells are separated by the inner and outer pillar cells which form the tunnel of Corti. IHC: inner hair cell, OHC: outer hair cell, IPhC: Inner phalangeal cell, IP: Inner pillar cell, OP: Outer pillar cell, DC: Deiters’ cell. Modified and reprinted from [16] under a CC BY license, with permission from Springer Nature, Understanding the cochlea (2017).

Figure 2.

Schematics of cellular reprogramming in the damaged organ of Corti. A) Introduction of a small molecule or siRNA (A) or viral vectors (B) to induce hair cell regeneration.