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Extracellular vesicles derived from human vestibular schwannomas associated with poor hearing damage cochlear cells
- Source :
- Neuro-Oncology. :now099
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
Abstract
- Background Vestibular schwannoma (VS) is a tumor of the vestibular nerve that transmits balance information from the inner ear to the brain. Sensorineural hearing loss occurs in 95% of patients with these tumors, but the cause of this loss is not well understood. We posit a role of VS-secreted extracellular vesicles (EVs) as a major contributing factor in cochlear nerve damage. Methods Using differential centrifugation, we isolated EVs from VS cell line HEI-193 and primary cultured human VS cells from patients with good hearing or poor hearing. The EVs were characterized using a Nanosight device and transmission electron microscopy and by extracting their RNA content. The EVs' effects on cultured murine spiral ganglion cells and organotypic cochlear cultures were studied using a transwell dual-culture system and by direct labeling of EVs with PKH-67 dye. EV-induced changes in cochlear cells were quantified using confocal immunohistochemistry. Transfection of VS cells with a green fluorescent protein-containing plasmid was confirmed with reverse transcription PCR. Results Human VS cells, from patients with poor hearing, produced EVs that could damage both cultured murine cochlear sensory cells and neurons. In contrast, EVs derived from VS cells from patients with good hearing did not damage the cultured cochlear cells. Conclusions This is the first report on EVs derived from VSs and on the capacity of EVs from VSs from patients with hearing loss to selectively damage cochlear cells, thereby identifying a potential novel mechanism of VS-associated sensorineural hearing loss.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Hearing loss
Hearing Loss, Sensorineural
Acoustic neuroma
Extracellular Vesicles
Mice
03 medical and health sciences
0302 clinical medicine
Basic and Translational Investigation
Cell Line, Tumor
Hair Cells, Auditory
otorhinolaryngologic diseases
medicine
Animals
Humans
Inner ear
030223 otorhinolaryngology
Cochlea
Spiral ganglion
business.industry
Neuroma, Acoustic
Transfection
Anatomy
Middle Aged
medicine.disease
Vestibular nerve
medicine.anatomical_structure
Oncology
RNA
Female
Sensorineural hearing loss
sense organs
Neurology (clinical)
medicine.symptom
Spiral Ganglion
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15235866 and 15228517
- Database :
- OpenAIRE
- Journal :
- Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....6bfb523a617751e8436ce32672c1abb8
- Full Text :
- https://doi.org/10.1093/neuonc/now099