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Extracellular vesicles derived from human vestibular schwannomas associated with poor hearing damage cochlear cells.
Soares, Vitor Y R; Atai, Nadia A; Fujita, Takeshi; Dilwali, Sonam; Sivaraman, Sarada; Landegger, Lukas D; Hochberg, Fred H; Oliveira, Carlos A P C; Bahmad, Fayez; Breakefield, Xandra O; Stankovic, Konstantina M.
Afiliación
  • Soares VY; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Atai NA; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Fujita T; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Dilwali S; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Sivaraman S; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Landegger LD; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Hochberg FH; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Oliveira CA; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Bahmad F; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Breakefield XO; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
  • Stankovic KM; Department of Otolaryngology, Eaton Peabody Laboratories, Massachusetts Eye and Ear, Boston, Massachusetts (V.Y.R.S., T.F., S.D., L.D.L., K.M.S.); Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts (V.Y.R.S., T.F., L.D.L., K.M.S.); Health Science Program and Departm
Neuro Oncol ; 18(11): 1498-1507, 2016 11.
Article en En | MEDLINE | ID: mdl-27194145
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ganglio Espiral de la Cóclea / Neuroma Acústico / Vesículas Extracelulares / Pérdida Auditiva Sensorineural Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Middle aged Idioma: En Revista: Neuro Oncol Asunto de la revista: NEOPLASIAS / NEUROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ganglio Espiral de la Cóclea / Neuroma Acústico / Vesículas Extracelulares / Pérdida Auditiva Sensorineural Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans / Middle aged Idioma: En Revista: Neuro Oncol Asunto de la revista: NEOPLASIAS / NEUROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido