Effect of epithelial stem cell transplantation on noise-induced hearing loss in adult mice.
Noise trauma in mammals can result in damage to multiple epithelial cochlear cell types, producing permanent hearing loss. Here we investigate whether epithelial stem cell transplantation can ameliorate noise-induced hearing loss in mice. Epithelial stem/progenitor cells isolated from adult mouse tongue displayed extensive proliferation in vitro as well as positive immunolabelling for the epithelial stem cell marker p63. To examine the functional effects of cochlear transplantation of these cells, mice were exposed to noise trauma and the cells were transplanted via a lateral wall cochleostomy 2 days post-trauma. Changes in auditory function were assessed by determining auditory brainstem response (ABR) threshold shifts 4 weeks after stem cell transplantation or sham surgery. Stem/progenitor cell transplantation resulted in a significantly reduced permanent ABR threshold shift for click stimuli compared to sham-injected mice, as corroborated using two distinct analyses. Cell fate analyses revealed stem/progenitor cell survival and integration into suprastrial regions of the spiral ligament. These results suggest that transplantation of adult epithelial stem/progenitor cells can attenuate the ototoxic effects of noise trauma in a mammalian model of noise-induced hearing loss.
Hearing Research Group, Neuroscience Program, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Jeremy M
JM
Sullivan
Mauricio A
MA
Cohen
Sonali R
SR
Pandit
Raguwinder S
RS
Sahota
Alexander A
AA
Borecki
Sharon
S
Oleskevich
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000473:pathology / Q000601:surgery*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology / Q000637:transplantation*; D005260:Female; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009416:Nerve Regeneration / Q000502:physiology; D010641:Phenotype; D020127:Recovery of Function / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014059:Tongue / Q000166:cytology / Q000473:pathology / Q000502:physiology