title: Cisplatin exposure damages resident stem cells of the mammalian inner ear.
abstract: BACKGROUND
  Cisplatin is a widely used chemotherapeutic agent that can also cause ototoxic injury. One potential treatment for cisplatin-induced hearing loss involves the activation of endogenous inner ear stem cells, which may then produce replacement hair cells. In this series of experiments, we examined the effects of cisplatin exposure on both hair cells and resident stem cells of the mouse inner ear.
  
  
  RESULTS
  Treatment for 24 hr with 10 µM cisplatin caused significant loss of hair cells in the mouse utricle, but such damage was not evident until 4 days after the cisplatin exposure. In addition to killing hair cells, cisplatin treatment also disrupted the actin cytoskeleton in remaining supporting cells, and led to increased histone H2AX phosphorylation within the sensory epithelia. Finally, treatment with 10 µM cisplatin appeared to have direct toxic effects on resident stem cells in the mouse utricle. Exposure to cisplatin blocked the proliferation of isolated stem cells and prevented sphere formation when those cells were maintained in suspension culture.
  
  
  CONCLUSIONS
  The results suggest that inner ear stem cells may be injured during cisplatin ototoxicity, thus limiting their ability to mediate sensory repair.
authors.affiliation: Department of Otolaryngology, Washington University School of Medicine, Saint Louis, Missouri.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Slattery
authors.forename: Kazuo
authors.initials: K
authors.lastname: Oshima
authors.forename: Stefan
authors.initials: S
authors.lastname: Heller
authors.forename: Mark E
authors.initials: ME
authors.lastname: Warchol
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002945:Cisplatin / Q000009:adverse effects*; D007758:Ear, Inner / Q000166:cytology / Q000187:drug effects* / Q000196:embryology*; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects / Q000196:embryology
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: H2AX; chemotherapy; hair cell; ototoxicity; regeneration; supporting cell