Enhanced Auditory Neuron Survival Following Cell-Based BDNF Treatment in the Deaf Guinea Pig

Exogenous neurotrophin delivery to the deaf cochlea can prevent deafness-induced auditory neuron degeneration, however, we have previously reported that these survival effects are rapidly lost if the treatment stops. In addition, there are concerns that current experimental techniques are not safe enough to be used clinically. Therefore, for such treatments to be clinically transferable, methods of neurotrophin treatment that are safe, biocompatible and can support long-term auditory neuron survival are necessary. Cell transplantation and gene transfer, combined with encapsulation technologies, have the potential to address these issues. This study investigated the survival-promoting effects of encapsulated BDNF over-expressing Schwann cells on auditory neurons in the deaf guinea pig. In comparison to control (empty) capsules, there was significantly greater auditory neuron survival following the cell-based BDNF treatment. Concurrent use of a cochlear implant is expected to result in even greater auditory neuron survival, and provide a clinically relevant method to support auditory neuron survival that may lead to improved speech perception and language outcomes for cochlear implant patients

Experimental Cohorts.

<p>Summary of experimental cohorts used in the study. Animals received implantations of either encapsulated BDNF-Schwann cells (eBDNF-SC) or empty capsules (control), and survived for either two or four weeks post-implantation.</p

Alginate capsules <i>in vitro</i>.

<p>(A) Alginate capsules containing BDNF-Schwann cells and (B) empty control capsules. Capsules are 500–600 µm in diameter. Scale bar = 250 µm.</p

Alginate capsules <i>in vivo</i>.

<p>(A) Histological section showing two alginate capsules containing clusters of BDNF-Schwann cells (asterix), in the basal region of the deaf guinea pig cochlea. One capsule was damaged during the histological processing, leading to rupture of the capsule wall (arrow). The large cochleostomy required for insertion of the capsules is outlined, and a vigorous tissue response is apparent in this area. It should be noted that the tissue response was typically localised to the region of the cochleostomy and there was no fibrous tissue in the more apical regions of the cochlea. (B) A higher magnification image showing a capsule containing BDNF-Schwann cells within the basal turn of the deaf guinea pig cochlea. The capsule walls are indicated by arrowheads. ST = scala tympani; SM = scala media; SV = scala vestibuli; RC = Rosenthal's canal.</p

The effects of cell-based neurotrophin treatment on auditory neuron survival in the deaf guinea pig.

<p>Implantation of encapsulated BDNF-Schwann cells (eBDNF-SCs) resulted in enhanced auditory neuron survival in comparison to empty capsules, over both two and four weeks (* <i>P</i><0.05). The number of surviving auditory neurons was calculated as an average across all cochlear turns.</p

Photomicrographs showing auditory neurons in Rosenthal's canal for each of the experimental cohorts.

<p>Histological sections show Rosenthal's canal in the lower basal turn of the deaf guinea pig cochlea implanted with either encapsulated BDNF-Schwann cells or empty control capsules, for either two or four weeks. Auditory neurons were identified and counted based upon the presence of an identifiable cell soma and a clear nucleus and nucleolus. Examples are indicated by arrow heads. There are more auditory neurons in cochleae implanted with encapsulated BDNF-Schwann cells than in cochleae receiving empty capsule control implants.</p