Human Fetal Auditory Stem Cells Can Be Expanded In Vitro and Differentiate Into Functional Auditory Neurons and Hair Cell-Like Cells

Chen, Wei; Johnson, Stuart L.; Marcotti, Walter; Andrews, Peter W.; Moore, H. D. M.; Rivolta, Marcelo N.

doi:10.1002/stem.62

Cited by 76 publications

(60 citation statements)

References 39 publications

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“…Of these studies, two have reported the use of human stem cells for auditory neuron replacement [11,12], and this will eventually be critical for translation of this therapy into clinical practice. In developing a cell replacement therapy for hearing loss, donor stem/progenitor cells must also be electrically active and capable of organized outgrowth of processes, including forming synapses on appropriate cells/tissues in the peripheral and central auditory system [13,14].…”

mentioning

confidence: 99%

“…Several laboratories have now explored the possibility of using stem cells to replace auditory neurons, which progressively degenerate after hearing loss [3][4][5][6][7][8][9][10][11][12]. Of these studies, two have reported the use of human stem cells for auditory neuron replacement [11,12], and this will eventually be critical for translation of this therapy into clinical practice.…”

mentioning

confidence: 99%

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An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

Nayagam

Edge²,

Needham³

et al. 2013

Stem Cells and Development

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In mammals, the sensory hair cells and auditory neurons do not spontaneously regenerate and their loss results in permanent hearing impairment. Stem cell therapy is one emerging strategy that is being investigated to overcome the loss of sensory cells after hearing loss. To successfully replace auditory neurons, stem cell-derived neurons must be electrically active, capable of organized outgrowth of processes, and of making functional connections with appropriate tissues. We have developed an in vitro assay to test these parameters using cocultures of developing cochlear explants together with neural progenitors derived from human embryonic stem cells (hESCs). We found that these neural progenitors are electrically active and extend their neurites toward the sensory hair cells in cochlear explants. Importantly, this neurite extension was found to be significantly greater when neural progenitors were predifferentiated toward a neural crest-like lineage. When grown in coculture with hair cells only (denervated cochlear explants), stem cell-derived processes were capable of locating and growing along the hair cell rows in an en passant-like manner. Many presynaptic terminals (synapsin 1-positive) were observed between hair cells and stem cell-derived processes in vitro. These results suggest that differentiated hESC-derived neural progenitors may be useful for developing therapies directed at auditory nerve replacement, including complementing emerging hair cell regeneration therapies.

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confidence: 99%

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confidence: 99%

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

Nayagam

Edge²,

Needham³

et al. 2013

Stem Cells and Development

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show abstract

“…To increase cell proliferation, growth factors were being used. Growth factors such as EGF, IGF, BFGF, and N-2® and B-27® supplements (Gibco) were used and reported to enhance the growth of these cells [18,26] . Auditory cells cultured with the supplementation of the growth factors EGF, IGF, BFGF, and N-2® and B-27® supplements in this study showed a significantly higher proliferation rate than cells without the supplementation of additional growth factors.…”

Section: Discussionmentioning

confidence: 99%

Effect of Growth Factor Supplementation on the Hair Cell Specific Markers of Cells Harvested from Basilar Membrane

Ubaidah

Chua²,

Ami

et al. 2015

Int Adv Otol

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OBJECTIVE:Loss of auditory hair cells is a major cause of deafness. The presence of auditory progenitor cells in the inner ear raises the hope for mammalian inner ear cell regeneration. In this study, we aimed to investigate the effect of growth factor supplementations, namely a combination of epidermal growth factor (EGF), insulin-like growth factor (IGF), and beta (β)-fibroblast growth factor (βFGF), on the expression of hair cell-specific markers by cells harvested from the cochlear membrane. This would provide an insight into the capability of these cells to differentiate into hair cells. MATERIALS and METHODS:EGF, IGF, and βFGF were supplemented into the culture medium. The cells were evaluated by morphology, growth kinetic, gene expression, and protein expression. RESULTS:The cultured cells of mouse basilar membrane were spindle shaped. Growth factors-enriched medium promotes a significantly higher proliferative activity than the basic culture medium but did not alter the cell morphology. Growth factors-enriched medium did not show any significant differences in the protein expression of the hair cell-specific markers myosin VIIa and calretinin and the stem-cell marker nestin. Gene expression analysis showed that the expression of the hair cell-specific genes myosin VIIa and calretinin as well as the stem cell genes nestin, Rex1, and Sox2 was reduced after the cells were passaged in the growth factor-supplemented medium. Cells in the basic medium expressed a significantly higher level of hair cell-specific genes at certain passages. CONCLUSION:Growth factor supplementation could not maintain the expression of hair cell-specific markers by cells obtained from the cochlear membrane.

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“…Three types of stem cells have been successfully differentiated into cell types that can be transplanted to improve SNHL: embryonic stem cells, adult inner ear stem cells, and neuronal stem cells. 84 Transplant of these cells presents a unique problem given the accessibility and size of the structures involved as well as the complicated relationship between cell types. Injection approaches are similar to those used for gene therapy and include round window, 85 lateral semicircular canal, 86 posterior semicircular canal, 87 cochlear lateral wall, 86,88 internal auditory meatus, 89 and modiolus.…”

Section: Stem Cell Therapy For Sensorineural Hearing Lossmentioning

confidence: 99%

On the Distant Horizon—Medical Therapy for Sensorineural Hearing Loss

Kelly

Lalwani

2015

Otolaryngologic Clinics of North America

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Human Fetal Auditory Stem Cells Can Be Expanded In Vitro and Differentiate Into Functional Auditory Neurons and Hair Cell-Like Cells

Cited by 76 publications

References 39 publications

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

An In Vitro Model of Developmental Synaptogenesis Using Cocultures of Human Neural Progenitors and Cochlear Explants

Effect of Growth Factor Supplementation on the Hair Cell Specific Markers of Cells Harvested from Basilar Membrane

On the Distant Horizon—Medical Therapy for Sensorineural Hearing Loss

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