Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans

Warchol, Mark E.; Lambert, Paul R.; Goldstein, Bradley J.; Forge, Andrew; Corwin, Jeffrey T.

doi:10.1126/science.8456285

Cited by 464 publications

(350 citation statements)

References 9 publications

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“…Perhaps the most notable difference between hair cells of the utricle and those of the mammalian organ of Corti is that the vestibular system has some capacity to regenerate hair cells Warchol et al, 1993). Despite these differences, vestibular hair cells have proven useful in tracking the cellular mechanisms underlying ototoxicity.…”

Section: Introductionmentioning

confidence: 99%

The adult mouse utricle as an in vitro preparation for studies of ototoxic-drug-induced sensory hair cell death

Cunningham

2006

Brain Research

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Sensory hair cells of the inner ear are susceptible to death from a variety of stresses including aging, noise trauma, genetic disorders, and exposure to certain therapeutic drugs. Ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic agent cisplatin. This is a short technical report describing the dissection and culture of the adult mouse utricle. This in vitro preparation allows for detailed studies of ototoxic drug-induced hair cell death in an adult mammalian system. In addition, this preparation allows for examination of the effects of specific gene products through the use of transgenic and knockout mouse models.

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Section: Introductionmentioning

confidence: 99%

The adult mouse utricle as an in vitro preparation for studies of ototoxic-drug-induced sensory hair cell death

Cunningham

2006

Brain Research

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“…Progressive hearing loss is common and most forms of deafness are irreversible. A low level of regeneration has been observed in mammalian vestibular epithelia Warchol et al 1993), for which attempts to establish cell lines have already been made Zheng et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Auditory hair cell precursors immortalized from the mammalian inner ear

Rivolta

Grix

Lawlor

et al. 1998

Proc. R. Soc. Lond. B

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Mammalian auditory hair cells are few in number, experimentally inaccessible, and do not proliferate postnatally or in vitro. Immortal cell lines with the potential to di¡erentiate into auditory hair cells would substantially facilitate auditory research, drug development, and the isolation of critical molecules involved in hair cell biology. We have established two conditionally immortal cell lines that express at least ¢ve characteristic hair cell markers. These markers are the transcription factor Brn3.1, the a9 subunit of the acetylcholine receptor, the stereociliary protein ¢mbrin and the myosins VI and VIIA. These hair cell precursors permit functional studies of cochlear genes and in the longer term they will provide the means to explore therapeutic methods of stimulating auditory hair cell regeneration.

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“…Assembling evidences support the hypothesis that Atoh1 is the determinant factor that drive stem cell differentiation and development. All the auditory and vestibular hair cells were absent in Atoh1 deficient mice, 2 4 and ectopic re-introduction of wild-type Atoh1 restored the hair cell fate within both the pro-sensory domain and non-sensory regions of the cochlea. 25 In line with these observations, our data demonstrated that Celastrol enhanced neuronal-like cell identity in the inner ear stem cell population as well as their electrophysiological function, which was highly likely to be mediated by the up-regulation of Atoh1.…”

Section: Discussionmentioning

confidence: 92%

“…Although the modest regenerative capacity has been observed in rodent vestibular sensory epithelia, 4 no hair cell regeneration occurred in adult mammalian cochlea at all. The endeavor to activate the regenerative capacity for medical purpose has been disappointing so far, which partially attributes to highly differentiated and specified cells in the delicate architecture of human auditory system.…”

Section: Introductionmentioning

confidence: 95%

Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells

Han

Cong

et al. 2018

Organogenesis

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We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.

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Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans

Cited by 464 publications

References 9 publications

The adult mouse utricle as an in vitro preparation for studies of ototoxic-drug-induced sensory hair cell death

The adult mouse utricle as an in vitro preparation for studies of ototoxic-drug-induced sensory hair cell death

Auditory hair cell precursors immortalized from the mammalian inner ear

Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells

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