Transplantation of neural stem cells into explants of Rat inner ear

Fujino, Kiyohisa; Kim, Taesoo; Nishida, Akiko; Nakagawa, Takayuki; Omori, Koichi; Naito, Yasushi; Ito, Juichi

doi:10.1080/03655230310016717

Cited by 12 publications

(9 citation statements)

References 6 publications

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“…In addition to cell replacement therapies, NSCs may have the ability to control or cure damage by being able to secrete trophic factors or cytokines (Iguchi et al, 2003; Fujino et al, 2004; Hakuba et al, 2005). Iguchi et al demonstrated that, once NSCs were transplanted into the inner ear, most of them differentiated into glial cells and spontaneously produced GDNF and BDNF in the cochlea (Iguchi et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Neural stem cells secrete factors that promote auditory cell proliferation via a leukemia inhibitory factor signaling pathway

Chen

Hsin

Sytwu

et al. 2010

J of Neuroscience Research

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The capacity for perpetual self-renewal is one of the main characteristics of stem cells. Little is known about the effect of embryonic neural stem cell (NSC)-secreted factors on auditory cell proliferation in vitro. In the present work, two auditory cell types were cultured in the presence of NSC-secreted molecules and were evaluated in vitro. Our results demonstrated that both cell viability and cell proliferation were significantly enhanced upon treatment with NSC conditioned medium, which contains significantly elevated levels of leukemia inhibitory factor (LIF) secreted by NSCs. The NSC conditioned medium not only activated the expression of leukemia inhibitory factor receptor in House Ear Institute-organ of Corti 1 cells but also up-regulated the LIF downstream signal transducers and activators of transcription (STAT) 1 and STAT3. Blocking either the LIF signaling pathway with neutralizing antibodies or the downstream Janus kinase (JAK)/STAT pathway with JAK2 inhibitor AG490 resulted in a dose-dependent inhibition of cell proliferation, suggesting that NSC-secreted molecules promote auditory cell survival via the regulatory LIF/JAK/STAT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Neural stem cells secrete factors that promote auditory cell proliferation via a leukemia inhibitory factor signaling pathway

Chen

Hsin

Sytwu

et al. 2010

J of Neuroscience Research

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“…Regardless of the remarkable plasticity of neural stem cells, inner earderived stem cells and their derivatives are probably most suitable for use in transplantation experiments to replace lost hair cells because the inner ear-derived spheres contain cells that readily differentiate into hair cell-like cells in vitro and in vivo (Li et al 2004a). One of the major obstacles that stem cell transplantation technology must overcome to repair damaged mammalian cochleae is the generation of hair cells in the organ of Corti in vivo, and despite some observations of neural stem cell survival and occasional expression of hair cell markers (Fujino et al 2004;Parker and Cotanche 2004;Tateya et al 2003), no robust regimen has been developed hitherto that allows the study of functional replacement of lost hair cells with stem cells. Nevertheless, the development of new surgical procedures and the exploration of stem cell types other than neural stem cells will hopefully result in more studies toward determining the potential of cochlear stem cell therapy.…”

Section: Introductionmentioning

confidence: 99%

Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Senn

Oshima

Teo

et al. 2007

JARO

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Potential treatment strategies of neurodegenerative and other diseases with stem cells derived from nonembryonic tissues are much less subjected to ethical criticism than embryonic stem cell-based approaches. Here we report the isolation of inner ear stem cells, which may be useful in cell replacement therapies for hearing loss, after protracted postmortem intervals. We found that neonatal murine inner ear tissues, including vestibular and cochlear sensory epithelia, display remarkably robust cellular survival, even 10 days postmortem. Similarly, isolation of sphere-forming stem cells was possible up to 10 days postmortem. We detected no difference in the proliferation and differentiation potential between stem cells isolated directly after death and up to 5 days postmortem. At longer postmortem intervals, we observed that the potency of sphere-derived cells to spontaneously differentiate into mature cell types diminishes prior to the cells losing their potential for self-renewal. Three-week-old mice also displayed sphere-forming stem cells in all inner ear tissues investigated up to 5 days postmortem. In summary, our results demonstrate that postmortem murine inner ear tissue is suited for isolation of stem cells.

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“…Transfection of the transcription factor Math1 ( Atoh1 ) into the ears of adult guinea pigs in vivo has produced exciting results with evidence of significant functional recovery (Kawamoto et al ., 2003; Izumikawa et al ., 2005). Cell transplantation is in its infancy (Ito et al ., 2001; Tateya et al ., 2003; Fujino et al ., 2004; Kojima et al ., 2004; Lopez‐Schier, 2004; Nakagawa & Ito, 2004; Parker & Cotanche, 2004; Sakamoto et al ., 2004; Tamura et al ., 2004) and is likely to be much more difficult to achieve with hair cells than with SGNs due to the highly specialized structure of the organ of Corti (Holley, 2002). Neuronal implants into the central auditory pathways have led to some functional recovery (Ito et al ., 1999).…”

Section: Introductionmentioning

confidence: 99%

Differentiation of an auditory neuronal cell line suitable for cell transplantation

Nicholl¹,

Kneebone²,

Davies

et al. 2005

Eur J of Neuroscience

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The auditory neuroblast cell line US/VOT-N33 (N33), which is conditionally immortal, was studied as an in vitro model for the differentiation of spiral ganglion neurons (SGNs) and as a candidate for cell transplantation in rodents. It expresses numerous molecular markers characteristic of auditory neuroblasts, including the transcription factors GATA3, NeuroD, Brn3a and Islet1, as well as the neuronal cytoskeletal protein beta3-tubulin. It displays active migratory behaviour in vitro and in vivo. In the presence of the fibroblast growth factors FGF1 or FGF2 it differentiates bipolar morphologies similar to those of native SGNs. In coculture with neonatal cochlear tissue it is repelled from epithelial surfaces but not from native SGNs, alongside which it extends parallel neuronal processes. When injected into the retina in vivo, EGFP-labelled N33 cells were traced for 1-2 weeks and migrated rapidly within the subretinal space. Cells that found their way into the retinal ganglion cell layer extended multiple processes but did not express beta3-tubulin. The ability of N33 to migrate, to differentiate, to localize with native SGNs in vitro and to survive in vivo suggests that they provide an effective model for SGN differentiation and for cell transplantation into the ear.

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Transplantation of neural stem cells into explants of Rat inner ear

Cited by 12 publications

References 6 publications

Neural stem cells secrete factors that promote auditory cell proliferation via a leukemia inhibitory factor signaling pathway

Neural stem cells secrete factors that promote auditory cell proliferation via a leukemia inhibitory factor signaling pathway

Robust Postmortem Survival of Murine Vestibular and Cochlear Stem Cells

Differentiation of an auditory neuronal cell line suitable for cell transplantation

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