title: Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats.
abstract: OBJECTIVE
  In this study, we aimed to elucidate the restorative effects of olfactory epithelium neural stem cells (oe-NSCs) implantation on noise-induced hearing loss and establish their mechanism of action.
  
  
  METHODS
  To model hearing loss, rats were subjected to consecutive seven-day noise exposure. Then, oe-NSCs were implanted into cochlear tissue by retroauricular approach. Auditory brainstem response (ABR) method was used to evaluate the hearing function. Immunohistochemical staining was utilized to determine cell survival and migration of oe-NSCs. After IL-1β stimulation, nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4 levels were evaluated in oe-NSCs. The protective action of oe-NSCs against hydrogen peroxide-induced cell injury was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).
  
  
  RESULTS
  oe-NSCs implantation into cochlear tissues ameliorated the noise-induced hearing impairment (p<0.05). After implantation, green fluorescent cells were observed in an even suspension in the lymph fluid of the cochlea, and 65% of the GFP(+) cells reached the cochlear duct wall three days after implantation, but did not expand to the Corti-organ. After IL-1β stimulation, olfactory epithelial stem cell increased their secretion of NGF and NT-3 (p<0.05), but not that of NT-4. TUNEL assay results revealed that oe-NSCs co-culturing with injured neurons reduced the apoptotic cell death induced by hydrogen peroxide.
  
  
  CONCLUSIONS
  After transplantation into the inner ear, oe-NSCs not only survived, but also migrated around the spiral ganglion neurons (SGNs) in Rosenthal's canal (RC). Hearing loss induced by noise exposure was restored after oe-NSCs implantation. Mechanically, oe-NSCs secreted NGF and NT-3, which likely contributed to the prevention of neuronal injury. This study provides novel data in support of the effective action of implanted oe-NSCs in the restoration of noise-induced hearing loss in a rat model.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, No. 463 Military Hospital, Shenyang, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Shan
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yue-Yang
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qi-Lei
authors.initials: QL
authors.lastname: Tao
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: fanjingping_1003@163.com.
authors.forename: Jing-Ping
authors.initials: JP
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D002478:Cells, Cultured; D003051:Cochlea / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem; D034381:Hearing Loss / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D058953:Neural Stem Cells / Q000637:transplantation*; D009474:Neurons / Q000473:pathology; D020933:Neurotrophin 3 / Q000378:metabolism; D009622:Noise / Q000009:adverse effects*; D009831:Olfactory Mucosa / Q000166:cytology*; D017207:Rats, Sprague-Dawley; D013136:Spiral Ganglion / Q000473:pathology
chemical_list: D020933:Neurotrophin 3; D020932:Nerve Growth Factor
keywords: Cell transplantation; NIHL; Olfactory epithelium neural stem cells