Cellular studies of auditory hair cell regeneration in birds

Stone, Jennifer S.; Rubel, Edwin W.

doi:10.1073/pnas.97.22.11714

Cited by 99 publications

(77 citation statements)

References 160 publications

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“…In birds, ototoxic lesions that deplete hair cells, leave behind differentiated supporting cells and regeneration occurs spontaneously (Cotanche, 1999;Stone et al, 2000;Stone et al, 1998). A more severe lesion that also influences the supporting cells has been accomplished with noise (Cotanche et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Response of the flat cochlear epithelium to forced expression of Atoh1

et al. 2008

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Following hair cell elimination in severely traumatized cochleae, differentiated supporting cells are often replaced by a simple epithelium with cuboidal or flat appearance. Atoh1 (previously Math1) is a basic helix-loop-helix transcription factor critical to hair cell differentiation during mammalian embryogenesis. Forced expression of Atoh1 in the differentiated supporting cell population can induce transdifferentiation leading to hair cell regeneration. Here we examined the outcome of adenovirus mediated over-expression of Atoh1 in the non-sensory cells of the flat epithelium. We determined that seven days after unilateral elimination of hair cells with neomycin, differentiated supporting cells are absent, replaced by a flat epithelium. Nerve processes were also missing from the auditory epithelium, with the exception of infrequent looping nerve processes above the habenula perforata. We then inoculated an adenovirus vector with Atoh1 insert into the scala media of the deafened cochlea. The inoculation resulted in upregulation of Atoh1 in the flat epithelium. However, two months after the inoculation, Atoh1-treated ears did not exhibit clear signs of hair cell regeneration. Combined with previous data on induction of supporting cell to hair cell transdifferentiation by forced expression of Atoh1, these results suggest that the presence of differentiated supporting cells in the organ of Corti is necessary for transdifferentiation to occur.

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Section: Discussionmentioning

confidence: 99%

Response of the flat cochlear epithelium to forced expression of Atoh1

et al. 2008

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“…Supporting cells are also likely to play a role in regeneration of damaged hair cells, as seen in other species (Baird et al, 2000;Stone and Rubel, 2000). Supporting cells not only emit factors required for hair cell survival, they apparently receive feedback from hair cells to monitor hair cell status.…”

Section: Supporting Cell Functionmentioning

confidence: 99%

“…Hair cell death then disrupts the feedback signal and triggers changes in one or more adjacent supporting cells, leading to a regenerative response. In all vertebrates (although not in the mammalian cochlea), hair cell regeneration can occur by either of two mechanisms (Baird et al, 2000;Stone and Rubel, 2000): Supporting cells can directly trans-differentiate into hair cells with no intervening cell division or can undergo asymmetric cell division to generate hair cells and new supporting cells. Supporting cells can also divide symmetrically to yield two new supporting cells.…”

Section: Supporting Cell Functionmentioning

confidence: 99%

Development of the zebrafish inner ear

Whitfield

Riley

Chiang

et al. 2002

Developmental Dynamics

212

186

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Recent years have seen a renaissance of investigation into the mechanisms of inner ear development. Genetic analysis of zebrafish has contributed significantly to this endeavour, with several dramatic advances reported over the past year or two. Here, we review the major findings from recent work in zebrafish. Several cellular and molecular mechanisms have been elucidated, including the signaling pathways controlling induction of the otic placode, morphogenesis and patterning of the otic vesicle, and elaboration of functional attributes of inner ear.

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“…The discovery that hair cells of the avian basilar papilla (BP), the functional equivalent of the mammalian organ of Corti, are regenerated after preexisting hair cells have been destroyed (Corwin and Cotanche 1988;Ryals and Rubel 1988;Warchol and Corwin 1996) has stimulated much interest in the possibility of hair cell regeneration therapy in mammals (Staecker and Van De Water 1998). The continuous formation of cochlear sensory epithelial cells with and without insult to the auditory system has also been demonstrated in the lower vertebrate inner ear, but not in mammals (Cotanche and Lee 1994;Stone and Rubel 2000;Reng et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

Hildebrand

Dahl

Hardman

et al. 2005

JARO

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The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment.

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Cellular studies of auditory hair cell regeneration in birds

Cited by 99 publications

References 160 publications

Response of the flat cochlear epithelium to forced expression of Atoh1

Response of the flat cochlear epithelium to forced expression of Atoh1

Development of the zebrafish inner ear

Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

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