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Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies

The sensory epithelia of the mammalian inner ear enable sound and movement to be perceived. Damage to these epithelia can cause irreversible sensorineural hearing loss and vestibular dysfunction because they lack regenerative capacity. The human inner ear cannot be biopsied without causing permanent...

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Detalles Bibliográficos
Autores principales: Connolly, Keeva, Gonzalez-Cordero, Anai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621662/
https://www.ncbi.nlm.nih.gov/pubmed/36331565
http://dx.doi.org/10.1242/dmm.049593
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author Connolly, Keeva
Gonzalez-Cordero, Anai
author_facet Connolly, Keeva
Gonzalez-Cordero, Anai
author_sort Connolly, Keeva
collection PubMed
description The sensory epithelia of the mammalian inner ear enable sound and movement to be perceived. Damage to these epithelia can cause irreversible sensorineural hearing loss and vestibular dysfunction because they lack regenerative capacity. The human inner ear cannot be biopsied without causing permanent damage, significantly limiting the tissue samples available for research. Investigating disease pathology and therapeutic developments have therefore traditionally relied on animal models, which often cannot completely recapitulate the human otic systems. These challenges are now being partly addressed using induced pluripotent stem cell-derived cultures, which generate the sensory epithelial-like tissues of the inner ear. Here, we review how pluripotent stem cells have been used to produce two-dimensional and three-dimensional otic cultures, the strengths and limitations of these new approaches, and how they have been employed to investigate genetic and acquired forms of audiovestibular dysfunction. This Review provides an overview of the progress in pluripotent stem cell-derived otic cultures thus far, focusing on their applications in disease modelling and therapeutic trials. We survey their current limitations and future directions, highlighting their prospective utility for high-throughput drug screening and developing personalised medicine approaches.
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spelling pubmed-106216622023-11-03 Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies Connolly, Keeva Gonzalez-Cordero, Anai Dis Model Mech Review The sensory epithelia of the mammalian inner ear enable sound and movement to be perceived. Damage to these epithelia can cause irreversible sensorineural hearing loss and vestibular dysfunction because they lack regenerative capacity. The human inner ear cannot be biopsied without causing permanent damage, significantly limiting the tissue samples available for research. Investigating disease pathology and therapeutic developments have therefore traditionally relied on animal models, which often cannot completely recapitulate the human otic systems. These challenges are now being partly addressed using induced pluripotent stem cell-derived cultures, which generate the sensory epithelial-like tissues of the inner ear. Here, we review how pluripotent stem cells have been used to produce two-dimensional and three-dimensional otic cultures, the strengths and limitations of these new approaches, and how they have been employed to investigate genetic and acquired forms of audiovestibular dysfunction. This Review provides an overview of the progress in pluripotent stem cell-derived otic cultures thus far, focusing on their applications in disease modelling and therapeutic trials. We survey their current limitations and future directions, highlighting their prospective utility for high-throughput drug screening and developing personalised medicine approaches. The Company of Biologists Ltd 2022-11-04 /pmc/articles/PMC10621662/ /pubmed/36331565 http://dx.doi.org/10.1242/dmm.049593 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Review
Connolly, Keeva
Gonzalez-Cordero, Anai
Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
title Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
title_full Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
title_fullStr Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
title_full_unstemmed Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
title_short Modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
title_sort modelling inner ear development and disease using pluripotent stem cells – a pathway to new therapeutic strategies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621662/
https://www.ncbi.nlm.nih.gov/pubmed/36331565
http://dx.doi.org/10.1242/dmm.049593
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