title: Combining cell-based therapies and neural prostheses to promote neural survival.
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 cats were 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.
authors: The Bionics Institute, 384-388 Albert Street, East Melbourne 3002, Australia. awise@bionicsinstitute.org
authors: Andrew K
authors: AK
authors: Wise
authors: James B
authors: JB
authors: Fallon
authors: Alison J
authors: AJ
authors: Neil
authors: Lisa N
authors: LN
authors: Pettingill
authors: Marilyn S
authors: MS
authors: Geaney
authors: Stephen J
authors: SJ
authors: Skinner
authors: Robert K
authors: RK
authors: Shepherd
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002415:Cats; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D019929:Cochlear Implantation / Q000379:methods*; D003638:Deafness / Q000188:drug therapy* / Q000601:surgery*; D004558:Electric Stimulation / Q000379:methods; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D008297:Male; D009414:Nerve Growth Factors / Q000627:therapeutic use; D058117:Neural Prostheses; D016900:Neurofilament Proteins
chemical_list: D009414:Nerve Growth Factors; D016900:Neurofilament Proteins