Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Senn, Pascal; Oshima, Koichiro; Teo, Dawn Tju Wei; Grimm, Christian; Heller, Stefan

doi:10.1007/s10162-007-0079-6

Cited by 46 publications

(56 citation statements)

References 18 publications

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“…Cochlear cell-derived spheres have been isolated and characterized by several laboratories and we noticed a considerable diversity in the reported morphology of spheres derived from inner ear sensory epithelium preparations (compare Li et al 2003;Oshima et al 2007;Savary et al 2007;Savary et al 2008;Senn et al 2007;Zhai et al 2005;Zhang et al 2007). This observation raised the question about the origin and the propagation/differentiation potential of the different sphere types that grow from the neonatal organ of Corti.…”

Section: Introductionmentioning

confidence: 93%

“…Cells were replated in sphere culture medium for 3-5 days to obtain the next generation. This method is feasible for the propagation of inner earderived spheres for up to ten generations (Li et al 2003;Oshima et al 2007;Savary et al 2008;Senn et al 2007). Specific analyses were conducted with solid spheres harvested after 3-4 days in vitro (DIV), with transitional spheres collected after 4-6 DIV, and with hollow spheres picked after 6-7 DIV, unless indicated differently.…”

Section: Cell Dissociation and Sphere Generationmentioning

confidence: 99%

“…2). We have previously shown that the vast majority of spheres that form in nonadherent low-density cultures are clonal, i.e., they were generated from single cells (Li et al 2003;Senn et al 2007). Based on light microscopic criteria, we classified three distinct sphere types.…”

Section: Different Sphere Morphologies Arise From Neonatal Cochlear Smentioning

confidence: 99%

“…Nevertheless, the remnant of the once powerful regenerative ability can be detected in the mammalian adult vestibular sensory epithelia as well as in the neonatal cochlea. Particularly, it has been possible to isolate self-renewing progenitor cells from these organs and to use the progeny of these cells to generate hair cell-like cells in vitro and in vivo (Li et al 2003;Oshima et al 2007;Savary et al 2007;Savary et al 2008;Senn et al 2007;White et al 2006;Zhai et al 2005;Zhang et al 2007). These inner earderived stem/progenitor cells are probably well-suited for proof-of-principle experiments aimed to replace lost hair cells in the organ of Corti, if the hurdles of cell delivery and proper cell homing could be overcome.…”

Section: Introductionmentioning

confidence: 99%

“…Sphereforming otic stem/progenitor cells display a distinct capacity to divide in nonadherent culture conditions, which results in the formation of clonal floating colonies (spheres). These spheres can be propagated, the sphere-derived cells express marker genes of the developing ear and nervous system, and sphere cells are capable of differentiating into a variety of different cell types, including supporting and hair cell-like cells (Li et al 2003;Oshima et al 2007;Savary et al 2008;Senn et al 2007;Zhai et al 2005;Zhang et al 2007). Sphere-forming otic progenitor cells are not only an excellent tool for in vitro developmental studies but they are also an important cell source for transplantation studies into damaged inner ears of animal models with the long-term objective of developing cell-based replacement therapies.…”

Section: Introductionmentioning

confidence: 99%

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Stem/Progenitor Cells Derived from the Cochlear Sensory Epithelium Give Rise to Spheres with Distinct Morphologies and Features

Diensthuber

Oshima

Heller

2009

JARO

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Nonmammalian vertebrates regenerate lost sensory hair cells by means of asymmetric division of supporting cells. Inner ear or lateral line supporting cells in birds, amphibians, and fish consequently serve as bona fide stem cells resulting in high regenerative capacity of hair cell-bearing organs. Hair cell regeneration does not happen in the mammalian cochlea, but cells with proliferative capacity can be isolated from the neonatal cochlea. These cells have the ability to form clonal floating colonies, so-called spheres, when cultured in nonadherent conditions. We noticed that the sphere population derived from mouse cochlear sensory epithelium cells was heterogeneous, consisting of morphologically distinct sphere types, hereby classified as solid, transitional, and hollow. Cochlear sensory epithelium-derived stem/progenitor cells initially give rise to small solid spheres, which subsequently transition into hollow spheres, a change that is accompanied by epithelial differentiation of the majority of sphere cells. Only solid spheres, and to a lesser extent, transitional spheres, appeared to harbor self-renewing stem cells, whereas hollow spheres could not be consistently propagated. Solid spheres contained significantly more rapidly cycling Pax-2-expressing presumptive otic progenitor cells than hollow spheres. Islet-1, which becomes upregulated in nascent sensory patches, was also more abundant in solid than in hollow spheres. Likewise, hair cell-like cells, characterized by the expression of multiple hair cell markers, differentiated in significantly higher numbers in cell populations derived from solid spheres. We conclude that cochlear sensory epithelium cell populations initially give rise to small solid spheres that have self-renewing capacity before they subsequently convert into hollow spheres, a process that is accompanied by loss of stemness and reduced ability to spontaneously give rise to hair celllike cells. Solid spheres might, therefore, represent the most suitable sphere type for cell-based assays or animal model transplantation studies aimed at development of cell replacement therapies.

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Section: Introductionmentioning

confidence: 93%

Section: Cell Dissociation and Sphere Generationmentioning

confidence: 99%

Section: Different Sphere Morphologies Arise From Neonatal Cochlear Smentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stem/Progenitor Cells Derived from the Cochlear Sensory Epithelium Give Rise to Spheres with Distinct Morphologies and Features

Diensthuber

Oshima

Heller

2009

JARO

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Progenitor Cells from the Adult Human Inner Ear

Senn

Mina

Volkenstein

et al. 2019

The Anatomical Record

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Loss of inner ear hair cells leads to incurable balance and hearing disorders because these sensory cells do not effectively regenerate in humans. A potential starting point for therapy would be the stimulation of quiescent progenitor cells within the damaged inner ear. Inner ear progenitor/stem cells, which have been described in rodent inner ears, would be principal candidates for such an approach. Despite the identification of progenitor cell populations in the human fetal cochlea and in the adult human spiral ganglion, no proliferative cell populations with the capacity to generate hair cells have been reported in vestibular and cochlear tissues of adult humans. The present study aimed at filling this gap by isolating colony‐forming progenitor cells from surgery‐ and autopsy‐derived adult human temporal bones in order to generate inner ear cell types in vitro. Sphere‐forming and mitogen‐responding progenitor cells were isolated from vestibular and cochlear tissues. Clonal spheres grown from adult human utricle and cochlear duct were propagated for a limited number of generations. When differentiated in absence of mitogens, the utricle‐derived spheres robustly gave rise to hair cell‐like cells, as well as to cells expressing supporting cell‐, neuron‐, and glial markers, indicating that the adult human utricle harbors multipotent progenitor cells. Spheres derived from the adult human cochlear duct did not give rise to hair cell‐like or neuronal cell types, which is an indication that human cochlear cells have limited proliferative potential but lack the ability to differentiate into major inner ear cell types. Anat Rec, 303:461–470, 2020. © 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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Deafferentiation‐associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain‐derived neurotrophic factor and acidic fibroblast growth factor

Glueckert

Bitsche

Miller

et al. 2008

J of Comparative Neurology

132

125

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Deafferentation of the auditory nerve from loss of sensory cells is associated with degeneration of nerve fibers and spiral ganglion neurons (SGN). SGN survival following deafferentation can be enhanced by application of neurotrophic factors (NTF), and NTF can induce the regrowth of SGN peripheral processes. Cochlear prostheses could provide targets for regrowth of afferent peripheral processes, enhancing neural integration of the implant, decreasing stimulation thresholds, and increasing specificity of stimulation. The present study analyzed distribution of afferent and efferent nerve fibers following deafness in guinea pigs using specific markers (parvalbumin for afferents, synaptophysin for efferent fibers) and the effect of brain derived neurotrophic factor (BDNF) in combination with acidic fibroblast growth factor (aFGF). Immediate treatment following deafness was compared with 3-week-delayed NTF treatment. Histology of the cochlea with immunohistochemical techniques allowed quantitative analysis of neuron and axonal changes. Effects of NTF were assessed at the light and electron microscopic levels. Chronic BDNF/aFGF resulted in a significantly increased number of afferent peripheral processes in both immediate- and delayed-treatment groups. Outgrowth of afferent nerve fibers into the scala tympani were observed, and SGN densities were found to be higher than in normal hearing animals. These new SGN might have developed from endogenous progenitor/stem cells, recently reported in human and mouse cochlea, under these experimental conditions of deafferentation-induced stress and NTF treatment. NTF treatment provided no enhanced maintenance of efferent fibers, although some synaptophysin-positive fibers were detected at atypical sites, suggesting some sprouting of efferent fibers.

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Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Cited by 46 publications

References 18 publications

Stem/Progenitor Cells Derived from the Cochlear Sensory Epithelium Give Rise to Spheres with Distinct Morphologies and Features

Stem/Progenitor Cells Derived from the Cochlear Sensory Epithelium Give Rise to Spheres with Distinct Morphologies and Features

Progenitor Cells from the Adult Human Inner Ear

Deafferentiation‐associated changes in afferent and efferent processes in the guinea pig cochlea and afferent regeneration with chronic intrascalar brain‐derived neurotrophic factor and acidic fibroblast growth factor

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