Functional evaluation of a cell replacement therapy in the inner ear.
OBJECTIVE
Cell replacement therapy in the inner ear will contribute to the functional recovery of hearing loss.


BACKGROUND
Cell replacement therapy is a potentially powerful approach to replace degenerated or severely damaged spiral ganglion neurons. This study aimed at stimulating the neurite outgrowth of the implanted neurons and enhancing the potential therapeutic of inner ear cell implants.


METHODS
Chronic electrical stimulation (CES) and exogenous neurotrophic growth factor (NGF) were applied to 46 guinea pigs transplanted with embryonic dorsal root ganglion (DRG) neurons 4 days postdeafening. The animals were evaluated with the electrically evoked auditory brainstem responses (EABRs) at experimental Days 7, 11, 17, 24, and 31. The animals were euthanized at Day 31, and the inner ears were dissected for immunohistochemistry investigation.


RESULTS
Implanted DRG cells, identified by enhanced green fluorescent protein fluorescence and a neuronal marker, were found close to Rosenthal canal in the adult inner ear for up to 4 weeks after transplantation. Extensive neurite projections clearly, greater than in nontreated animals, were observed to penetrate the bony modiolus and reach the spiral ganglion region in animals supplied with CES and/or NGF. There was, however, no significant difference in the thresholds of EABRs between DRG-transplanted animals supplied with CES and/or NGF and DRG-transplanted animals without CES or NGF supplement.


CONCLUSIONS
The results suggest that CES and/or NGF can stimulate neurite outgrowth from implanted neurons, although based on EABR measurement, these interventions did not induce functional connections to the central auditory pathway. Additional time or novel approaches may enhance functional responsiveness of implanted cells in the adult cochlea.
Hu
Zhengqing
Z
Center for Hearing and Communication Research, Karolinska Institute, Stockholm, Sweden. zh@med.wayne.edu
Ulfendahl
Mats
M
Prieskorn
Diane M
DM
Olivius
Petri
P
Miller
Josef M
JM
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D017690:Cell Transplantation / Q000379:methods*; D007758:Ear, Inner / Q000166:cytology* / Q000502:physiology; D004558:Electric Stimulation; D016057:Evoked Potentials, Auditory, Brain Stem; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology / Q000637:transplantation; D049452:Green Fluorescent Proteins; D006168:Guinea Pigs; D034381:Hearing Loss / Q000628:therapy*; D007150:Immunohistochemistry; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration; D016501:Neurites / Q000378:metabolism; D014183:Transplantation, Heterologous
D015415:Biomarkers; D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins