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

Article Highlights

• Limited spontaneous hair cell regeneration occurs in the neonatal mouse cochlea and in the neonatal and adult mouse utricle.

• As in non-mammalian species, supporting cells in mammalian sensory organs can act as hair cell progenitors.

• Cochlear supporting cells rapidly lose the ability to regenerate hair cells as the organ matures.

• Direct cellular reprogramming is efficacious in inducing ectopic hair cells in the neonatal cochlea; however, results have been mixed in the mature organ.

• The overall efficacy of a combination approach to induce hair cell regeneration in the mature cochlea remains low.

This box summarizes key points contained in the article.

Acknowledgments

We thank Z. Sayyid and T. Jan for critical reading and C. Gralapp for graphical illustration.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work has been funded by Garnett Passe and Rodney Williams Memorial Foundation, Lucile Packard Foundation for Children’s Health Stanford, the NIH National Center for Translation Sciences – Clinical and Translational Sciences Awards program UL1TR001085 and NIH/NIDCD RO1DC013910, California Institute in Regenerative Medicine RN3-06529.