Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats

Ya-Ping Xu; Xiao-Dong Shan; Yue-Yang Liu; Yu Pu; Cheng-Yu Wang; Qi-Lei Tao; Yue Deng; Yin Cheng; Jing-Ping Fan

doi:10.1016/j.neulet.2016.01.016

Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats

Neurosci Lett. 2016 Mar 11:616:19-25. doi: 10.1016/j.neulet.2016.01.016. Epub 2016 Jan 14.

Authors

Ya-Ping Xu¹, Xiao-Dong Shan², Yue-Yang Liu¹, Yu Pu¹, Cheng-Yu Wang¹, Qi-Lei Tao¹, Yue Deng¹, Yin Cheng¹, Jing-Ping Fan³

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
² Department of Otolaryngology Head and Neck Surgery, No. 463 Military Hospital, Shenyang, China.
³ Department of Otolaryngology Head and Neck Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China. Electronic address: fanjingping_1003@163.com.

PMID: 26777425
DOI: 10.1016/j.neulet.2016.01.016

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.

Conclusion: 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.

Keywords: Cell transplantation; NIHL; Olfactory epithelium neural stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Cell Movement
Cells, Cultured
Cochlea / pathology
Evoked Potentials, Auditory, Brain Stem
Hearing Loss / pathology
Hearing Loss / physiopathology
Hearing Loss / therapy*
Male
Nerve Growth Factor / metabolism
Neural Stem Cells / transplantation*
Neurons / pathology
Neurotrophin 3 / metabolism
Noise / adverse effects*
Olfactory Mucosa / cytology*
Rats, Sprague-Dawley
Spiral Ganglion / pathology

Substances

Neurotrophin 3
Nerve Growth Factor