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Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants.

Abstract

The auditory apparatus of the inner ear does not show turnover of sensory hair cells (HCs) in adult mammals; in contrast, there are many observations supporting low-level turnover of vestibular HCs within the balance organs of mammalian inner ears. This low-level renewal of vestibular HCs exists during normal conditions and it is further enhanced after trauma-induced loss of these HCs. The main process for renewal of HCs within mammalian vestibular epithelia is a conversion/transdifferentiation of existing supporting cells (SCs) into replacement HCs.In earlier studies using long-term organ cultures of postnatal rat macula utriculi, HC loss induced by gentamicin resulted in an initial substantial decline in HC density followed by a significant increase in the proportion of HCs to SCs indicating the production of replacement HCs. In the present study, using the same model of ototoxic damage to study renewal of vestibular HCs, we focus on the ultrastructural characteristics of SCs undergoing transdifferentiation into new HCs. Our objective was to search for morphological signs of SC plasticity during this process. In the utricular epithelia, we observed immature HCs, which appear to be SCs transdifferentiating into HCs. These bridge SCs have unique morphological features characterized by formation of foot processes, basal accumulation of mitochondria, and an increased amount of connections with nearby SCs. No gap junctions were observed on these transitional cells. The tight junction seals were morphologically intact in both control and gentamicin-exposed explants. Anat Rec, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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  • Authors+Show Affiliations

    ,

    Department of Clinical Sciences, Otolaryngology, University of Umeå, Umeå, Sweden.

    ,

    Cochlear Implant Research Program, Department of Otolaryngology, University of Miami Ear Institute, University of Miami Miller School of Medicine, Miami, Florida.

    ,

    Department of Epidemiology and Global Health, University of Umeå, Umeå, Sweden.

    Department of Clinical Sciences, Otolaryngology, University of Umeå, Umeå, Sweden.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31090209

    Citation

    Werner, Mimmi, et al. "Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants." Anatomical Record (Hoboken, N.J. : 2007), 2019.
    Werner M, Van De Water TR, Stenlund H, et al. Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants. Anat Rec (Hoboken). 2019.
    Werner, M., Van De Water, T. R., Stenlund, H., & Berggren, D. (2019). Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants. Anatomical Record (Hoboken, N.J. : 2007), doi:10.1002/ar.24148.
    Werner M, et al. Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants. Anat Rec (Hoboken). 2019 May 14; PubMed PMID: 31090209.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Ultrastructural Characterization of Stem Cell-Derived Replacement Vestibular Hair Cells Within Ototoxin-Damaged Rat Utricle Explants. AU - Werner,Mimmi, AU - Van De Water,Thomas R, AU - Stenlund,Hans, AU - Berggren,Diana, Y1 - 2019/05/14/ PY - 2018/03/01/received PY - 2018/08/23/revised PY - 2018/09/07/accepted PY - 2019/5/16/pubmed PY - 2019/5/16/medline PY - 2019/5/16/entrez KW - morphology KW - plasticity KW - rat KW - regeneration KW - support cell KW - transdifferentiation KW - utricle KW - vestibular hair cell JF - Anatomical record (Hoboken, N.J. : 2007) JO - Anat Rec (Hoboken) N2 - The auditory apparatus of the inner ear does not show turnover of sensory hair cells (HCs) in adult mammals; in contrast, there are many observations supporting low-level turnover of vestibular HCs within the balance organs of mammalian inner ears. This low-level renewal of vestibular HCs exists during normal conditions and it is further enhanced after trauma-induced loss of these HCs. The main process for renewal of HCs within mammalian vestibular epithelia is a conversion/transdifferentiation of existing supporting cells (SCs) into replacement HCs.In earlier studies using long-term organ cultures of postnatal rat macula utriculi, HC loss induced by gentamicin resulted in an initial substantial decline in HC density followed by a significant increase in the proportion of HCs to SCs indicating the production of replacement HCs. In the present study, using the same model of ototoxic damage to study renewal of vestibular HCs, we focus on the ultrastructural characteristics of SCs undergoing transdifferentiation into new HCs. Our objective was to search for morphological signs of SC plasticity during this process. In the utricular epithelia, we observed immature HCs, which appear to be SCs transdifferentiating into HCs. These bridge SCs have unique morphological features characterized by formation of foot processes, basal accumulation of mitochondria, and an increased amount of connections with nearby SCs. No gap junctions were observed on these transitional cells. The tight junction seals were morphologically intact in both control and gentamicin-exposed explants. Anat Rec, 2019. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. SN - 1932-8494 UR - https://www.unboundmedicine.com/medline/citation/31090209/Ultrastructural_Characterization_of_Stem_Cell-Derived_Replacement_Vestibular_Hair_Cells_Within_Ototoxin-Damaged_Rat_Utricle_Explants L2 - https://doi.org/10.1002/ar.24148 DB - PRIME DP - Unbound Medicine ER -