Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig.
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Date
2015-01
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Abstract
The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the primary
auditory neurons (ANs) of the cochlea. However, ANs degenerate in deafness; the preservation of a robust AN
target population, in combination with advances in cochlear implant technology, may provide improved hearing
outcomes for cochlear implant patients. The exogenous delivery of neurotrophins such as brain-derived neurotrophic
factor (BDNF) and neurotrophin-3 iswell known to support AN survival in deafness, and cell-based therapies
provide a potential clinically viable option for delivering neurotrophins into the deaf cochlea. This study
utilized cells that were genetically modified to express BDNF and encapsulated in alginate microspheres, and
investigated AN survival in the deaf guinea pig following (a) cell-based neurotrophin treatment in conjunction
with chronic electrical stimulation from a cochlear implant, and (b) long-term cell-based neurotrophin delivery.
In comparison to deafened controls, there was significantly greater AN survival following the cell-based
neurotrophin treatment, and there were ongoing survival effects for at least six months. In addition, functional
benefits were observed following cell-based neurotrophin treatment and chronic electrical stimulation, with a
statistically significant decrease in electrically evoked auditory brainstem response thresholds observed during
the experimental period. This study demonstrates that cell-based therapies, in conjunction with a cochlear
implant, shows potential as a clinically transferable means of providing neurotrophin treatment to support AN
survival in deafness. This technology also has the potential to deliver other therapeutic agents, and to be used
in conjunction with other biomedical devices for the treatment of a variety of neurodegenerative conditions.
Description
Keywords
Deafness, BDNF, Cell Therapy, Cell Encapsulation, Cochlear Implant
Citation
Gillespie, L. N., Zanin, M. P. & Shepherd, R. K. Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig. Journal of Controlled Release 198, 26-34, 2015