Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear

Hu, Zhengqing; Wei, Daoyan; Johansson, Clas B.; Holmström, Niklas; Duan, Maoli; Frisén, Jonas; Ulfendahl, Mats

doi:10.1016/j.yexcr.2004.08.023

Cited by 153 publications

(132 citation statements)

References 41 publications

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“…The in vivo ototoxicity model was established by supplying gentamicin and/or morin into the mouse inner ear according to established procedures 21. Mice were randomly divided equally into three experimental groups ( n = 10 each): ( i ) control, 0 mg/kg gentamicin + 0 mg/kg morin hydrate; ( ii ) GM, 40 mg/kg gentamicin + 0 mg/kg morin hydrate; and ( iii ) GM+morin, 40 mg/kg gentamicin + 10 mg/kg morin hydrate.…”

Section: Methodsmentioning

confidence: 99%

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Jia

Zhang

et al. 2016

J Cellular Molecular Medi

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We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin‐induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss.

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Section: Methodsmentioning

confidence: 99%

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Jia

Zhang

et al. 2016

J Cellular Molecular Medi

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“…A portion of the surviving mESCs (not specified in the text) showed a neuronal phenotype based on neurofilament immunolabeling. Hu et al (2005) placed neural stem cells from the lateral wall of mouse lateral ventricle into normal or deafened guinea pig cochlea and found only a few reached a neuronal phenotype, based on TUJ1 (neuronal class III β-tubulin) immunostaining, with many showing a glial fated based on GFAP immunostaining. More recently, Parker et al (2007) used neural stem cells derived from mouse fetal cerebellum, placed into noise exposed mouse or guinea pig cochleae.…”

Section: Differentiation Into An Appropriate Phenotypementioning

confidence: 99%

“…Falk et al (2002) found that transduction of stem cells with Neurogenin 2 (Ngn2) induced over 90% towards a neuronal phenotype. Hu et al (2005) tested this approach in the cochlea, transfecting Ngn2 into neural stem cells prior to placement and found the number reaching a neuronal phenotype (based on immunostaining for TUJ1) increased from 15% to over 50%. Hu et al (2004) co-transplantated mouse ESCs and a neuronal co-graft of dorsal root ganglion tissue into guinea pig cochlea, to influence stem cell differentiation in vivo.…”

Section: Differentiation Into An Appropriate Phenotypementioning

confidence: 99%

Stem cell transplantation for auditory nerve replacement

2008

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The successful function of cochlear prostheses depends on activation of auditory nerve. The survival of auditory nerve neurons, however, can vary widely in candidates for cochlear implants and influence implant efficacy. Stem cells offer the potential for improving the function of cochlear prostheses and increasing the candidate pool by replacing lost auditory nerve. The first phase of studies for stem cell replacement of auditory nerve has examined the in vitro survival and differentiation as well as in vivo differentiation and survival of exogenous embryonic and tissue stem cells placed into scala tympani and/or modiolus. These studies are reviewed and new results on in vivo placement of B-5 mouse embryonic stem cells into scala tympani of the guinea pig cochleae with differentiation into a glutamatergic neuronal phenotype are presented. Research on the integration and connections of stem cell derived neurons in the cochlea is described. Finally, an alternative approach is considered, based on the use of endogenous progenitors rather than exogenous stem cells, with a review of promising findings that have identified stem cell-like progenitors in cochlear and vestibular tissues to provide the potential for auditory nerve replacement.

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“…Repopulation of lost SGNs with NSC-derived neurons may provide improvement of hearing rehabilitation. Previous studies have attempted to replace lost SGNs by transplanting neurons from other ganglia or stem cells from exogenous sources, such as embryonic stem cells and neural stem cells (42,43 and the transplantation of predifferentiated NSCs is more likely to provide an effective functional replacement. …”

Section: Discussionmentioning

confidence: 99%

“…Myosin VIIA-GFP mice were generated by using standard methods (21). Cells of the lateral ventricular layers were isolated and neurospheres were generated and cultured as previously described (42). Neuronal differentiation was enhanced with 2 M retinoic acid.…”

Section: Methodsmentioning

confidence: 99%

Cells of adult brain germinal zone have properties akin to hair cells and can be used to replace inner ear sensory cells after damage

Wei

Levic

Nie

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Auditory hair cell defect is a major cause of hearing impairment, often leading to spiral ganglia neuron (SGN) degeneration. The cell loss that follows is irreversible in mammals, because inner ear hair cells (HCs) have a limited capacity to regenerate. Here, we report that in the adult brain of both rodents and humans, the ependymal layer of the lateral ventricle contains cells with proliferative potential, which share morphological and functional characteristics with HCs. In addition, putative neural stem cells (NSCs) from the subventricular zone of the lateral ventricle can differentiate into functional SGNs. Also important, the NSCs can incorporate into the sensory epithelia, demonstrating their therapeutic potential. We assert that NSCs and edendymal cells can undergo an epigenetic functional switch to assume functional characteristics of HCs and SGNs. This study suggests that the functional plasticity of renewable cells and conditions that promote functional reprogramming can be used for cell therapy in the auditory setting.cochlea ͉ ependymal cells ͉ hearing restoration ͉ neural stem cells ͉ spiral ganglia neurons

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Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear

Cited by 153 publications

References 41 publications

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

Stem cell transplantation for auditory nerve replacement

Cells of adult brain germinal zone have properties akin to hair cells and can be used to replace inner ear sensory cells after damage

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