Spiral ganglion neurons (SGNs), the target cells of the
cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in
deafness. The preservation of a viable population of SGNs in
deafness can be achieved in animal models with exogenous application of
neurotrophins such as
brain-derived neurotrophic factor (
BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based
neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express
BDNF can support SGN survival in
deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based
neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii)
neurotrophins, in order to determine which variables may provide long-term
neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express
BDNF provided the most sustained
neurotrophin expression, with ongoing
BDNF expression for at least 30 weeks. In addition, the secreted
neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of
neurotrophins to the deafened cochlea to support SGN survival in
deafness.