Robust generation of new hair cells in the mature mammalian inner ear by adenoviral expression of Hath1.
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.
Shou
Jianyong
J
Department of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
Zheng
J Lisa
JL
Gao
Wei Qiang
WQ
D000256:Adenoviridae / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D003051:Cochlea / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D003714:Denervation; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D005822:Genetic Vectors / Q000627:therapeutic use; D005839:Gentamicins / Q000494:pharmacology; D018069:Hair Cells, Vestibular / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D034381:Hearing Loss / Q000628:therapy; D006801:Humans; D051381:Rats; D012038:Regeneration / Q000235:genetics*; D012444:Saccule and Utricle / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015837:Vestibular Diseases / Q000628:therapy
D000617:Aminoglycosides; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005839:Gentamicins; C500942:ATOH1 protein, human