Combining cell-based therapies and neural prostheses to promote neural survival
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Date
2011-10
Journal Title
Journal ISSN
Volume Title
Publisher
Springer
Abstract
Cochlear implants provide partial restoration of
hearing for profoundly deaf patients by electrically stimulating
spiral ganglion neurons (SGNs); however, these neurons
gradually degenerate following the onset of deafness. Although
the exogenous application of neurotrophins (NTs) can prevent
SGN loss, current techniques to administer NTs for long periods
of time have limited clinical applicability. We have used
encapsulated choroid plexus cells (NTCells; Living Cell
Technologies, Auckland, New Zealand) to provide NTs in a
clinically viable manner that can be combined with a cochlear
implant. Neonatal catswere deafened and unilaterally implanted
with NTCells and a cochlear implant. Animals received chronic
electrical stimulation (ES) alone, NTs alone, or combined NTs
and ES (ES + NT) for a period of as much as 8 months. The
opposite ear served as a deafened unimplanted control. Chronic
ES alone did not result in increased survival of SGNs or their
peripheral processes. NT treatment alone resulted in greater
SGN survival restricted to the upper basal cochlear region and
an increased density of SGN peripheral processes. Importantly,
chronic ES in combination with NTs provided significant SGN
survival throughout a wider extent of the cochlea, in addition to
an increased peripheral process density. Re-sprouting peripheral
processes were observed in the scala media and scala tympani,
raising the possibility of direct contact between peripheral
processes and a cochlear implant electrode array. We conclude
that cell-based therapy is clinically viable and effective in
promoting SGN survival for extended durations of cochlear
implant use. These findings have important implications for the
safe delivery of therapeutic drugs to the cochlea.
Description
Keywords
Cell Survival - Drug effects, Cochlear Implantation - Methods, Deafness - Drug therapy, Deafness - Surgery, Electric Stimulation - Methods, Evoked Potentials, Auditory, Brain Stem, Nerve Growth Factors - Therapeutic use, Neural Prostheses, Neurofilament Proteins, Tissue Therapy - Methods
Citation
Wise, A. K., Fallon, J. B., Neil, A. J., Pettingill, L. N., Geaney, M. S., Skinner, S. J., & Shepherd, R. K. (2011). Combining cell-based therapies and neural prostheses to promote neural survival. Neurotherapeutics, 8(4), 774-787.