Regeneration of Hair Cells from Endogenous Otic Progenitors in the Adult Mammalian Cochlea: Understanding Its Origins and Future Directions

Natalia Smith-Cortinez*, A Katherine Tan, Robert J Stokroos, Huib Versnel, Louise V Straatman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Sensorineural hearing loss is caused by damage to sensory hair cells and/or spiral ganglion neurons. In non-mammalian species, hair cell regeneration after damage is observed, even in adulthood. Although the neonatal mammalian cochlea carries regenerative potential, the adult cochlea cannot regenerate lost hair cells. The survival of supporting cells with regenerative potential after cochlear trauma in adults is promising for promoting hair cell regeneration through therapeutic approaches. Targeting these cells by manipulating key signaling pathways that control mammalian cochlear development and non-mammalian hair cell regeneration could lead to regeneration of hair cells in the mammalian cochlea. This review discusses the pathways involved in the development of the cochlea and the impact that trauma has on the regenerative capacity of the endogenous progenitor cells. Furthermore, it discusses the effects of manipulating key signaling pathways targeting supporting cells with progenitor potential to promote hair cell regeneration and translates these findings to the human situation. To improve hearing recovery after hearing loss in adults, we propose a combined approach targeting (1) the endogenous progenitor cells by manipulating signaling pathways (Wnt, Notch, Shh, FGF and BMP/TGFβ signaling pathways), (2) by manipulating epigenetic control, and (3) by applying neurotrophic treatments to promote reinnervation.

Original languageEnglish
Article number7840
Pages (from-to)1-23
Number of pages23
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - May 2023


  • Adult
  • Cochlea/metabolism
  • Hair Cells, Auditory/metabolism
  • Humans
  • Infant, Newborn
  • Neurogenesis
  • Signal Transduction
  • Spiral Ganglion
  • endogenous progenitor cells
  • re-innervation
  • inner ear regeneration


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