Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1

Mol Cell Neurosci. 2003 Jun;23(2):169-79. doi: 10.1016/s1044-7431(03)00066-6.

Abstract

Although hair cells regenerate spontaneously in birds and lower vertebrates following injury, there is yet no effective way to stimulate hair cell regeneration in mature mammalian inner ears. Here we report that a large number of hair cells are produced in the sensory epithelium of cultured adult rat utricular maculae, via adenovirus-mediated overexpression of Hath1, a human atonal homolog. The generation of new hair cells via Hath1 expression does not involve cell proliferation based on bromodeoxyuridine immunocytochemistry. Furthermore, using a similar approach, hair cells are regenerated following aminoglycoside injury in these cultures. These data show conclusively that mature mammalian inner ears have the competence to produce a large number of new hair cells. Local adenoviral gene therapy in the inner ear may be a potential approach to treatment of hearing and balance disorders.

MeSH terms

  • Adenoviridae / genetics
  • Aging / genetics
  • Aging / metabolism
  • Aminoglycosides / pharmacology
  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Division / physiology
  • Cells, Cultured
  • Cilia / metabolism
  • Cilia / ultrastructure
  • Cochlea / cytology
  • Cochlea / growth & development
  • Cochlea / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / therapeutic use
  • Denervation
  • Genetic Therapy / methods
  • Genetic Therapy / trends
  • Genetic Vectors / therapeutic use
  • Gentamicins / pharmacology
  • Hair Cells, Vestibular / cytology
  • Hair Cells, Vestibular / growth & development*
  • Hair Cells, Vestibular / metabolism
  • Hearing Loss / therapy
  • Humans
  • Rats
  • Regeneration / genetics*
  • Saccule and Utricle / cytology
  • Saccule and Utricle / growth & development*
  • Saccule and Utricle / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Vestibular Diseases / therapy

Substances

  • ATOH1 protein, human
  • Aminoglycosides
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Gentamicins