gms | German Medical Science

Objective: Loss of spiral ganglion cells in the inner ear cochlea results in irreversible hearing loss. Once damaged, the axons of the spiral ganglion cells show no spontaneous regeneration which leads to degeneration of the neurons themselves and other cell types in the auditory system. Nanofibres have been shown to have a promising therapeutic potential in the regeneration of the optic system of the CNS. Therefore they seem to be an interesting candidate to investigate for the regeneration of the cochlear nerve.

Methods: We established spiral ganglion stem cells, which could be propagated in a standard manner for in vitro screening of nanofibres. The nanofibres were synthesized with the following characteristics: amphiphile, pH neutral, in a gel state of aggregation and with different functional epitopes. For in vitro screening, we investigated various nanofibres for compatibility, axonal growth, differentiation pattern and survival rate by time dependent documentation and descriptive immunocytochemistry. Promising candidates were used for in vivo application.

A transection of the cochlear nerve in the cerebellopontine angle was performed in adult rats with a consequent electrophysiological verification of the lesion with acustic evoked potentials (AEP) (n=80). Directly after transaction, nanofibre-gels with active epitopes (treated group) and with an inactive epitope (sham treated group) were applied at the site of lesion and compared with animals that received no nanofibres (lesion-only group). Electrophysiological recordings were performed at different time points (pre and post surgery, 2, 4, 8 and 12 weeks). Eventually the animals were sacrificed after variable survival times (2, 4, 8 and 12 weeks) and for histological evaluation cryo sections were done.

Results: Several nanofibre-gels with active epitopes offered favourable in vitro conditions for survival, growth and differentiation for the investigated cells. The cells could be detected, differentiated into neurons and grow axons on the gel surface for up to 14 days of incubation. In vivo no electrophysiological evidence for regeneration was seen in the sham treated and the lesion-only groups. In some animals treated with active epitopes, reoccurrence of AEPs was observed. Further histological evidence of a possible regeneration is necessary.

Conclusions: Nanofibre-gels are suitable for the investigation of regeneration. Promising in vitro candidates have yet to prove their regenerational potential in vivo.