Induced Cochlear Hair Cell Regeneration & Recovery of Hearing after Acoustic Trauma - January 2013 -

Drug Enables Deafened Mice to Hear Again
www.cell.com/neuron/abstract/S...
Ref.: Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma Hellfireeuron, Volume 77, Issue 1, 58-69, 9 January 2013, DOI: 10.1016/j.neuron.2012.10.032
Highlights
•Sensory hair cell regeneration is demonstrated in an adult mammal
•Inhibition of Notch stimulates hair cell regeneration after acoustic trauma
•Hair cells are derived from transdifferentiation of cochlear supporting cells
•Frequency region of hearing recovery corresponds to area of hair cell replacement
Summary
Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a -secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor Atoh1 in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre-lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness.