Fibroblast-mediated delivery of GDNF induces neuronal-like outgrowth in PC12 cells

Hypothesis: Recombinantly modified cells deliver neurotrophic factors with the capacity to induce differentiation and the outgrowth of neurites of rat pheochromocytoma cells 12 (PC12) serving as a neuronal model. Background: The benefit of cochlea implant (CI) is depending, among other factors, on the number of surviving spiral ganglion neurons (SGN). Studies have shown that the external application of neurotrophic factors in combination with electrical stimulation increases the survival rate of SGN after ototrauma. Therefore, functionalization of electrodes with recombinantly modified cells providing neurotrophic factors to the SGN for inducing survival mechanisms may be an approach to realize drug delivery to the cochlea. Methods: Murine NIH3T3 cells were recombinantly modified with an infectious lentiviral monocistronic and bicistronic system to synthesize glial cell line-derived neurotrophic factor and the green fluorescent protein. Free glial cell line-derived neurotrophic factor from the supernatant of the modified NIH3T3 cells was added to rat PC 12, and the neuronal-like outgrowth was determined for 10 days. Results: A significant neuronal-like outgrowth appeared as early as Day 3 after the application of the supernatant. Conclusion: The results indicate that the established in vitro model represents a powerful basic model for determining signal pathways between neuronal-like processing PC12 cells and cellular drug delivery systems.