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Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea

BACKGROUND: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to...

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Autores principales: Taylor, Ruth R., Jagger, Daniel J., Forge, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267727/
https://www.ncbi.nlm.nih.gov/pubmed/22299045
http://dx.doi.org/10.1371/journal.pone.0030577
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author Taylor, Ruth R.
Jagger, Daniel J.
Forge, Andrew
author_facet Taylor, Ruth R.
Jagger, Daniel J.
Forge, Andrew
author_sort Taylor, Ruth R.
collection PubMed
description BACKGROUND: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. METHODOLOGY/PRINCIPAL FINDINGS: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca's, suggesting genetic background influences the rate of re-organisation. CONCLUSIONS/SIGNIFICANCE: The lack of dedifferentiation amongst supporting cells and their replacement by cells from the outer side of the organ of Corti are factors that may need to be considered in any attempt to promote endogenous hair cell regeneration. The variability of the cellular environment along an individual cochlea arising from patch-like generation of flat epithelium, and the possible variability between individuals resulting from genetic influences on the rate at which remodelling occurs may pose challenges to devising the appropriate regenerative therapy for a deaf patient.
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spelling pubmed-32677272012-02-01 Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea Taylor, Ruth R. Jagger, Daniel J. Forge, Andrew PLoS One Research Article BACKGROUND: Following the loss of hair cells from the mammalian cochlea, the sensory epithelium repairs to close the lesions but no new hair cells arise and hearing impairment ensues. For any cell replacement strategy to be successful, the cellular environment of the injured tissue has to be able to nurture new hair cells. This study defines characteristics of the auditory sensory epithelium after hair cell loss. METHODOLOGY/PRINCIPAL FINDINGS: Studies were conducted in C57BL/6 and CBA/Ca mice. Treatment with an aminoglycoside-diuretic combination produced loss of all outer hair cells within 48 hours in both strains. The subsequent progressive tissue re-organisation was examined using immunohistochemistry and electron microscopy. There was no evidence of significant de-differentiation of the specialised columnar supporting cells. Kir4.1 was down regulated but KCC4, GLAST, microtubule bundles, connexin expression patterns and pathways of intercellular communication were retained. The columnar supporting cells became covered with non-specialised cells migrating from the outermost region of the organ of Corti. Eventually non-specialised, flat cells replaced the columnar epithelium. Flat epithelium developed in distributed patches interrupting regions of columnar epithelium formed of differentiated supporting cells. Formation of the flat epithelium was initiated within a few weeks post-treatment in C57BL/6 mice but not for several months in CBA/Ca's, suggesting genetic background influences the rate of re-organisation. CONCLUSIONS/SIGNIFICANCE: The lack of dedifferentiation amongst supporting cells and their replacement by cells from the outer side of the organ of Corti are factors that may need to be considered in any attempt to promote endogenous hair cell regeneration. The variability of the cellular environment along an individual cochlea arising from patch-like generation of flat epithelium, and the possible variability between individuals resulting from genetic influences on the rate at which remodelling occurs may pose challenges to devising the appropriate regenerative therapy for a deaf patient. Public Library of Science 2012-01-27 /pmc/articles/PMC3267727/ /pubmed/22299045 http://dx.doi.org/10.1371/journal.pone.0030577 Text en Taylor et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Taylor, Ruth R.
Jagger, Daniel J.
Forge, Andrew
Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea
title Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea
title_full Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea
title_fullStr Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea
title_full_unstemmed Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea
title_short Defining the Cellular Environment in the Organ of Corti following Extensive Hair Cell Loss: A Basis for Future Sensory Cell Replacement in the Cochlea
title_sort defining the cellular environment in the organ of corti following extensive hair cell loss: a basis for future sensory cell replacement in the cochlea
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267727/
https://www.ncbi.nlm.nih.gov/pubmed/22299045
http://dx.doi.org/10.1371/journal.pone.0030577
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