Effect of GDNF on schwann cell differentiation and interaction with neurons in vitro

Abstract

Schwann cells (SCs) are known to provide chemical and physical cues to enhance regeneration following peripheral nerve injury, yet it remains to be shown the effect that specific SC phenotypes (motor or sensory) have on axonal regeneration and functional recovery. In particular, the difference between motor and sensory SC phenotypes may encourage specific motor or sensory axonal guidance in cell transplantation therapies. Thus, the goal of this study was to determine whether phenotypically matched combinations of neurons and SCs stimulate greater neurite extension over mismatched combinations and whether treatment with glial cell line-derived neurotrophic factor (GDNF) affects this SC-neuronal interaction. Our aim is to study the effects of secreted, soluble factors without the interference of cell-to-cell contact cues using microfluidic devices. By elimination of cell-cell contact, we can isolate soluble factors secreted by motor or sensory SCs and determine differential expression of growth factors that induce a particular response from phenotypically matched SCs. Results demonstrated statistically greater neurite extension when neurons were cultured with phenotypically matched SCs, however, mismatched cultures could be compensated for when SCs were pre-treated with GDNF. In addition, exogenous GDNF treatment increased endogenous GDNF mRNA and protein expression levels. As sensory autografts are often used to bridge motor nerve defects, motor axons may not regenerate correctly without transplantation of motor SCs. However, these results suggest that treatment of SCs with GDNF prior to transplantation could enhance their ability to promote proper reinnervation even with mismatched transplanted SCs or graft phenotypes.