Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma

Noise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery....

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Main Authors: Anna Rita Fetoni, Wanda eLattanzi, Sara Letizia Maria Eramo, Marta eBarba, Fabiola ePaciello, Chiara eMoriconi, Rolando eRolesi, Fabrizio eMichetti, Diana eTroiani, Gaetano ePaludetti
Format: Article
Language:English
Published: Frontiers Media S.A. 2014-10-01
Series:Frontiers in Cellular Neuroscience
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Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00334/full
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author Anna Rita Fetoni
Wanda eLattanzi
Wanda eLattanzi
Sara Letizia Maria Eramo
Marta eBarba
Fabiola ePaciello
Chiara eMoriconi
Rolando eRolesi
Fabrizio eMichetti
Diana eTroiani
Gaetano ePaludetti
author_facet Anna Rita Fetoni
Wanda eLattanzi
Wanda eLattanzi
Sara Letizia Maria Eramo
Marta eBarba
Fabiola ePaciello
Chiara eMoriconi
Rolando eRolesi
Fabrizio eMichetti
Diana eTroiani
Gaetano ePaludetti
author_sort Anna Rita Fetoni
collection DOAJ
description Noise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery. Several evidences indicate adipose-derived stem cells (ASCs) as promising tools in diversified regenerative medicine applications, due to the high degree of plasticity and trophic features.This study was aimed at identifying the path of in vivo cell migration and expression of trophic growth factors, upon ASC transplantation into the cochlea, following noise-induced injury. ASCs were isolated in primary culture from the adipose tissue of a guinea pig, transduced using a viral vector to express the green fluorescent protein, and implanted into the scala tympani of deafened animals. Auditory function was assessed 3 and 7 days after surgery. The expression of trophic growth factors was comparatively analyzed using real time PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to assess the in vivo localization and expression of trophic growth factors in ASCs and cochleae, 3 and 7 days following homologous implantation. ASC implantation did not modify auditory function. ASCs migrated from the perilymphatic to the endolymphatic compartment, during the analyzed time course. Upon noise exposure, the expression of chemokine ligands and receptors related to the PDGF, VEGF and TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo cell migration. Immunofluorescence confirmed the increased expression, which appeared to be further strengthened by ASC implantation.These results indicate that ASCs are able to migrate at the site of tissue damage and express trophic factors, upon intracochlear implantantion, providing an original proof of principle, which could pave the way for further developments of ASC-based treatments of deafness.
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spelling doaj.art-1baf377dcd4345a5aa457c5ddedb1e582022-12-21T19:31:08ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-10-01810.3389/fncel.2014.00334105855Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic traumaAnna Rita Fetoni0Wanda eLattanzi1Wanda eLattanzi2Sara Letizia Maria Eramo3Marta eBarba4Fabiola ePaciello5Chiara eMoriconi6Rolando eRolesi7Fabrizio eMichetti8Diana eTroiani9Gaetano ePaludetti10Università Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreLatium Musculoskeletal Tissue BankUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreUniversità Cattolica del Sacro CuoreNoise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery. Several evidences indicate adipose-derived stem cells (ASCs) as promising tools in diversified regenerative medicine applications, due to the high degree of plasticity and trophic features.This study was aimed at identifying the path of in vivo cell migration and expression of trophic growth factors, upon ASC transplantation into the cochlea, following noise-induced injury. ASCs were isolated in primary culture from the adipose tissue of a guinea pig, transduced using a viral vector to express the green fluorescent protein, and implanted into the scala tympani of deafened animals. Auditory function was assessed 3 and 7 days after surgery. The expression of trophic growth factors was comparatively analyzed using real time PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to assess the in vivo localization and expression of trophic growth factors in ASCs and cochleae, 3 and 7 days following homologous implantation. ASC implantation did not modify auditory function. ASCs migrated from the perilymphatic to the endolymphatic compartment, during the analyzed time course. Upon noise exposure, the expression of chemokine ligands and receptors related to the PDGF, VEGF and TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo cell migration. Immunofluorescence confirmed the increased expression, which appeared to be further strengthened by ASC implantation.These results indicate that ASCs are able to migrate at the site of tissue damage and express trophic factors, upon intracochlear implantantion, providing an original proof of principle, which could pave the way for further developments of ASC-based treatments of deafness.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00334/fullCochleaGene Expressiongrowth factorsnoise-induced hearing lossadipose-derived stem cells
spellingShingle Anna Rita Fetoni
Wanda eLattanzi
Wanda eLattanzi
Sara Letizia Maria Eramo
Marta eBarba
Fabiola ePaciello
Chiara eMoriconi
Rolando eRolesi
Fabrizio eMichetti
Diana eTroiani
Gaetano ePaludetti
Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma
Frontiers in Cellular Neuroscience
Cochlea
Gene Expression
growth factors
noise-induced hearing loss
adipose-derived stem cells
title Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma
title_full Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma
title_fullStr Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma
title_full_unstemmed Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma
title_short Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a guinea pig model of acoustic trauma
title_sort grafting and early expression of growth factors from adipose derived stem cells transplanted into the cochlea in a guinea pig model of acoustic trauma
topic Cochlea
Gene Expression
growth factors
noise-induced hearing loss
adipose-derived stem cells
url http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00334/full
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