Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells

We investigated whether treatment with brain-derived neurotrophic factor (BDNF), which is known to protect spiral ganglion cells (SGCs), could also protect hair cells (HCs) and supporting cells (SCs) in the organ of Corti of a guinea pig model of sensorineural hearing loss. Hearing loss was induced by administration of kanamycin/furosemide and two BDNF treatments were performed: (1) by gelatin sponge (BDNF-GS) with acute cochlear implantation (CI), and (2) through a mini-osmotic pump (BDNF-OP) with chronic CI. Outer HCs (OHCs), inner HCs (IHCs), Border, Phalangeal, Pillar, Deiters’, and Hensen’s cells were counted. The BDNF-GS cochleas had significantly fewer OHCs compared to the untreated ones, while the IHC and SC numbers did not differ between treated and untreated cochleas. The BDNF-OP group showed similar cell numbers to the untreated group. SGC packing density was not correlated with the total number of SCs for either BDNF group. Our data suggest that: (1) BDNF does not prevent cell death in the organ of Corti, and that the protection of SGCs could result from a direct targeting by BDNF; (2) BDNF might induce a different function/activity of the remaining cells in the organ of Corti (independently from cell number).

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The Presence of Neural Stem Cells and Changes in Stem Cell-Like Activity With Age in Mouse Spiral Ganglion Cells In Vivo and In Vitro

Clinical and Experimental Otorhinolaryngology ◽

10.21053/ceo.2018.00878 ◽

2018 ◽

Vol 11 (4) ◽

pp. 224-232 ◽

Cited By ~ 2

Author(s):

Byoung-San Moon ◽

Aswathy Ammothumkandy ◽

Naibo Zhang ◽

Lei Peng ◽

Albina Ibrayeva ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Neural Stem Cells ◽

Ganglion Cells ◽

Spiral Ganglion

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Electron Microscopic Findings in Presbycusic Degeneration of the Basal Turn of the Human Cochlea

Otolaryngology ◽

10.1177/019459987908700617 ◽

1979 ◽

Vol 87 (6) ◽

pp. 818-836 ◽

Cited By ~ 47

Author(s):

Joseph B. Nadol

Keyword(s):

Light Microscopy ◽

Hair Cells ◽

Basilar Membrane ◽

Ganglion Cells ◽

Nerve Fibers ◽

Degenerative Changes ◽

Supporting Cells ◽

Neural Degeneration ◽

Basal Turn ◽

Temporal Bones

Three human temporal bones with presbycusis affecting the basal turn of the cochlea were studied by light and electron microscopy. Conditions in two ears examined by light microscopy were typical of primary neural degeneration, with a descending audiometric pattern, loss of cochlear neurons in the basal turn, and preservation of the organ of Corti. Ultrastructural analysis revealed normal hair cells and marked degenerative changes of the remaining neural fibers, especially in the basal turn. These changes included a decrease in the number of synapses at the base of hair cells, accumulation of cellular debris in the spiral bundles, abnormalities of the dendritic fibers and their sheaths in the osseous spiral lamina, and degenerative changes in the spiral ganglion cells and axons. These changes were interpreted as an intermediate stage of degeneration prior to total loss of nerve fibers and ganglion cells as visualized by light microscopy. In the third ear the changes observed were typical of primary degeneration of hair and supporting cells in the basal turn with secondary neural degeneration. Additional observations at an ultrastructural level included maintenance of the tight junctions of the scala media despite loss of both hair and supporting cells, suggesting a capacity for cellular “healing” in the inner ear. Degenerative changes were found in the remaining neural fibers in the osseous spiral lamina. In addition, there was marked thickening of the basilar membrane in the basal turn, which consisted of an increased number of fibrils and an accumulation of amorphous osmiophilic material in the basilar membrane. This finding supports the concept that mechanical alterations may occur in presbycusis of the basal turn.

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Wnt1 from Cochlear Schwann Cells Enhances Neuronal Differentiation of Transplanted Neural Stem Cells in a Rat Spiral Ganglion Neuron Degeneration Model

Cell Transplantation ◽

10.3727/096368913x669761 ◽

2014 ◽

Vol 23 (6) ◽

pp. 747-760 ◽

Cited By ~ 10

Author(s):

Ya He ◽

Peng-Zhi Zhang ◽

Dong Sun ◽

Wen-Juan Mi ◽

Xin-Yi Zhang ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Neuronal Differentiation ◽

Schwann Cells ◽

Spiral Ganglion ◽

Ganglion Neuron ◽

Spiral Ganglion Neuron ◽

Neuron Degeneration

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Population and density of the bipolar ganglion cells in the cochlea of the harp seal (Pagophilus groenlandicus Erxleben, 1777)

Canadian Journal of Zoology ◽

10.1139/z76-222 ◽

1976 ◽

Vol 54 (11) ◽

pp. 1918-1926 ◽

Cited By ~ 5

Author(s):

F. Ramprashad

Keyword(s):

Hair Cells ◽

Ganglion Cells ◽

Spiral Ganglion ◽

Harp Seal ◽

Nerve Cell Body ◽

Continuous Ring ◽

Average Value ◽

Pagophilus Groenlandicus ◽

Sensory Hair Cells ◽

Two Peaks

The population and density of the bipolar ganglion cells were determined from serial horizontal sections and graphic reconstructions of the cochleas of five captive harp seals. The [Formula: see text]-turn spiral ganglion forms a continuous ring throughout its course except at the extreme basal end where it is narrowest. The nerve cell body is 25 μm long (16.1–38.8 μm) and 16 μm wide (10–24 μm). The average number of ganglion cells present was 57 185 (46 389 – 70 952), with a corrected total number of 52 000 ganglion cells. Two peaks are present in the density curve of the ganglion cells. The first was at 1–1.5 mm and the second at 20 mm, where 2620 cells/mm2 and 2250 cells/mm2 respectively are present.The ratio of total ganglion cells to total sensory hair cells was about 3:1. This ratio was not uniform throughout the length of the cochlea; it was 6:1 at 2–3 mm from the basal end and declined gradually to 3:1 at the apical end. The average total of ganglion cells in the harp seal exceeded the average value in humans, but did not exceed the values found in dolphins.

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In vitro induction and differentiation of newborn guinea pig hippocampus neural stem cells into cells resembling inner hair cells, using artificial perilymph

The Journal of Laryngology & Otology ◽

10.1017/s0022215111000922 ◽

2011 ◽

Vol 125 (8) ◽

pp. 771-775 ◽

Cited By ~ 1

Author(s):

Y Wang ◽

M-M Dong

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Hair Cell ◽

Hair Cells ◽

Guinea Pigs ◽

Bovine Serum ◽

Fetal Bovine Serum ◽

Specific Antibodies ◽

Fetal Bovine

AbstractObjective:To investigate whether artificial perilymph can induce neural stem cells, derived from the hippocampus of newborn guinea pigs, to differentiate into inner ear hair cells, in vitro.Methods:Primary neural stem cells derived from the hippocampus of newborn guinea pigs were incubated in medium containing either 10 per cent fetal bovine serum or 5, 10 or 15 per cent artificial perilymph, for three weeks. Differentiated cells were identified using immunofluorescence, Western blot and scanning electron microscopy.Results:Both fetal bovine serum and artificial perilymph induced the neural stem cells to differentiate into cells with hair-cell-specific antibodies.Conclusion:Neural stem cells can survive in both fetal bovine serum and artificial perilymph, and within these media can differentiate into cells with hair-cell-specific antibodies. This provides an experimental basis for transplantation of neural stem cells into the inner ear.

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Vesicular glutamate transporter 3 is strongly upregulated in cochlear inner hair cells and spiral ganglion cells of developing circling mice

Neuroscience Letters ◽

10.1016/j.neulet.2014.10.053 ◽

2015 ◽

Vol 584 ◽

pp. 320-324 ◽

Cited By ~ 4

Author(s):

Youngeun Lee ◽

Hak Rim Kim ◽

Seung Cheol Ahn

Keyword(s):

Hair Cells ◽

Ganglion Cells ◽

Spiral Ganglion ◽

Glutamate Transporter ◽

Vesicular Glutamate Transporter ◽

Inner Hair Cells

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Electron Microscope Observations on in Vitro Cultures of the Isolated Fowl Embryo Otocyst

The Journal of Cell Biology ◽

10.1083/jcb.5.2.263 ◽

1959 ◽

Vol 5 (2) ◽

pp. 263-268 ◽

Cited By ~ 58

Author(s):

I. Friedmann

Keyword(s):

Electron Microscope ◽

Hair Cells ◽

Ganglion Cells ◽

Sensory Epithelium ◽

In Vitro Cultures ◽

Supporting Cells ◽

Suitable Material ◽

Stage Of Development ◽

Self Differentiation

In vitro cultures of isolated fowl embryo otocysts were studied with the electron microscope. Hair cells of the developing organ of Corti and crista ampullaris have been examined with particular reference to the structure of the cilia and of the cell membrane. Two types of hair cells could be distinguished on the basis whether or not they possessed a "kinocilium" and "stereocilia," or "stereocilia" only. The cytoplasmic membranes were simple and there were no multiple vesicular layers in any of the hair cells. The supporting elements consisted of supporting cells flanking the hair cells, fibroblasts, and the cartilaginous otic capsule. Both the cochlear and vestibular sensory area showed rich innervation by mainly non-myelinated fibers with partial myelinization in others. There were well developed ganglion cells present. Bare axons penetrated the basement membrane and spread, amongst the supporting cells sheltering them, to the base of the hair cells where they formed bud-shaped nerve endings but, at the stage of development examined, no calyces. These in vitro cultures of the isolated fowl embryo otocyst provided convenient and suitable material for the electron microscope study of the sensory epithelium of the ear and revealed further that the isolated fowl embryo otocyst possesses great powers of self-differentiation also at the ultrastructural level.

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PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9980444 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Yanzhuo Zhang ◽

Zhe Lv ◽

Yudong Liu ◽

Huan Cao ◽

Jianwang Yang ◽

...

Keyword(s):

Hearing Loss ◽

Hair Cells ◽

Ganglion Cells ◽

Spiral Ganglion ◽

Cell Senescence ◽

Prolyl Isomerase ◽

Age Related ◽

Pin1 Protein

A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by H2O2 was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under H2O2 and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.

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