Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants

Werner, Mimmi; Water, Thomas R. Van De; Hammarsten, Peter; Arnoldsson, Göran; Berggren, Diana

doi:10.1016/j.heares.2014.12.011

Cited by 4 publications

(8 citation statements)

References 48 publications

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“…A more recent study by Warner-Czyz and colleagues also reported similar findings for self-esteem, where the 50 children and adolescents with hearing loss in the study had significantly higher ratings of self-esteem to hearing peers [25]. The children with hearing loss were aged eight to 18 years, aided using hearing aids or cochlear implants and had received listening and spoken language early intervention.…”

Section: Introductionsupporting

confidence: 52%

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Social inclusion for children with hearing loss in listening and spoken Language early intervention: an exploratory study

Sharpe

Phillips

Davis³

et al. 2017

BMC Pediatr

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BackgroundSocial inclusion is a common focus of listening and spoken language (LSL) early intervention for children with hearing loss. This exploratory study compared the social inclusion of young children with hearing loss educated using a listening and spoken language approach with population data.MethodsA framework for understanding the scope of social inclusion is presented in the Background. This framework guided the use of a shortened, modified version of the Longitudinal Study of Australian Children (LSAC) to measure two of the five facets of social inclusion (‘education’ and ‘interacting with society and fulfilling social goals’). The survey was completed by parents of children with hearing loss aged 4–5 years who were educated using a LSL approach (n = 78; 37% who responded). These responses were compared to those obtained for typical hearing children in the LSAC dataset (n = 3265).ResultsAnalyses revealed that most children with hearing loss had comparable outcomes to those with typical hearing on the ‘education’ and ‘interacting with society and fulfilling social roles’ facets of social inclusion.ConclusionsThese exploratory findings are positive and warrant further investigation across all five facets of the framework to identify which factors influence social inclusion.

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Section: Introductionsupporting

confidence: 52%

“…Communication skills (as rated by the participants), participant age, age of fitting of hearing aids or cochlear implants, duration of use and social engagement (e.g. participation in activities and friendships) were not found to be linked to self-esteem [25]. …”

Section: Introductionmentioning

confidence: 99%

Social inclusion for children with hearing loss in listening and spoken Language early intervention: an exploratory study

Sharpe

Phillips

Davis³

et al. 2017

BMC Pediatr

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“…129 For trans-differentiated hair cells to function properly, however, they must also integrate into their local microenvironment. Thus, even if the hurdle of trans-differentiation were overcome, other substantial challenges would remain.…”

Section: Discussionmentioning

confidence: 99%

Congenital hearing loss

Korver

Smith

Camp

et al. 2017

Nat Rev Dis Primers

422

310

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Congenital hearing loss (hearing loss present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing-screening programmes enable early detection; early intervention will prevent delays in speech and language development and have long-lasting beneficial effects on social and emotional development and quality of life. A hearing loss diagnosis is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision-making and guide prevention and (genetic) counseling. Management options include specific antimicrobial therapies, surgical treatment of cranio-facial abnormalities and hearing aids. An improved understanding of the pathophysiology and molecular mechanisms underlying hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.

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“…Observations of individual vestibular cells with some morphology signs characteristic for an HC and some morphology signs characteristic for an SC have been reported after trauma-induced HC-loss (Li and Forge, 1997;Werner et al, 2015). Cells that morphologically appear to be in an intermediate state between an SC and an HC have been reported to have stereocilia as an HC and basal extensions toward the basal membrane and sometimes seem to be covered apically by cytoplasmic extensions from neighboring SCs.…”

Section: Discussion Morphologic Characterization Of Hcsmentioning

confidence: 99%

“…HCs are highly differentiated sensory cells that have lost their ability to proliferate and damage to these sensory cells will therefore lead to impaired hearing and balance. In mammalian vestibular epithelia, but not in the cochlear epithelium, a limited spontaneous renewal of HCs can be induced by a trauma causing HC‐loss such as aminoglycoside exposure (Forge et al, ; Tanyeri et al, ; Forge et al, ; Berggren et al, ; Werner et al, ). The process contributing to the renewal of mammalian vestibular HCs after aminoglycoside exposure has been described as a direct transdifferentiation of SCs into HCs (Kawamoto et al, ; Lin et al, ; Burns and Stone, ).…”

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confidence: 99%

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

Werner

Water

Stenlund

et al. 2019

The Anatomical Record

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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, 303:506–515, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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Morphological and morphometric characterization of direct transdifferentiation of support cells into hair cells in ototoxin-exposed neonatal utricular explants

Cited by 4 publications

References 48 publications

Social inclusion for children with hearing loss in listening and spoken Language early intervention: an exploratory study

Social inclusion for children with hearing loss in listening and spoken Language early intervention: an exploratory study

Congenital hearing loss

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

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