title: Cell-gene delivery of brain-derived neurotrophic factor to the mouse inner ear.
abstract: Sensorineural hearing loss is a common disability, but treatment options are currently limited to cochlear implants and hearing aids. Studies are therefore being conducted to provide alternative means of biological therapy, including gene therapy. Safe and effective methods of gene delivery to the cochlea need to be developed to facilitate the clinical application of these therapeutic treatments for hearing loss. In this study, we examined the potential of cell-gene therapy with nonviral vectors for delivery of therapeutic molecules into the cochlea. NIH3T3 cells were transfected with the brain-derived neurotrophic factor (Bdnf) gene using lipofection and then transplanted into the mouse inner ear. Immunohistochemistry and Western blotting demonstrated the survival of grafted cells in the cochlea for up to 4 weeks after transplantation. No significant hearing loss was induced by the transplantation procedure. A Bdnf-specific enzyme-linked immunosorbent assay revealed a significant increase in Bdnf production in the inner ear following transplantation of engineered cells. These findings indicate that cell-gene delivery with nonviral vectors may be applicable for the local, sustained delivery of therapeutic molecules into the cochlea.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 606-8507 Kyoto, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okano
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kita
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Endo
authors.forename: Juichi
authors.initials: J
authors.lastname: Ito
mesh_terms: D000818:Animals; D001309:Auditory Threshold; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D017690:Cell Transplantation / Q000379:methods*; D003051:Cochlea / Q000166:cytology / Q000378:metabolism; D007758:Ear, Inner / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D006085:Graft Survival / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger