Evidence for cell‐contact factor involvement in neurite outgrowth of dorsal root ganglion neurons stimulated by Schwann cells

NEW FINDINGS: What is the central question of this study? Although the factors secreted from Schwann cells that promote axonal growth in the peripheral nervous system have been well studied, the effect of cell-contact factors on Schwann cells remains to be determined. What is the main finding and its importance? This study demonstrates that Schwann cells stimulate neurite outgrowth by direct contact with neurites and by secreting factors. Notably, the effect of cell-contact factors in neurite outgrowth is comparable to that of secreted factors, indicating that the identification of cell surface molecules on Schwann cells that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury. ABSTRACT: Schwann cells (SCs) play a variety of roles in the regeneration process after injury to the peripheral nervous system. The factors secreted from SCs that promote axonal growth have been well studied. However, the involvement of cell-contact factors on SCs remains to be determined. Here, we demonstrate a significant contribution of a cell-contact mechanism in the effect of SCs on promotion of neuronal outgrowth. Neurite outgrowth of adult sensory neurons from dorsal root ganglia was quantified during co-culture with adult SCs. Direct contact of SCs with neurons was eliminated by culturing SCs on an insert placed in the same well; this resulted in a 51% reduction in the length of neurite outgrowth. In addition, when dorsal root ganglion neurons were cultured on sparsely seeded SCs, neurons that made contact with SCs on their neurites had 118% longer neurites than neurons that lacked contacts with SCs. Collectively, these findings provide evidence that SCs stimulate neurite outgrowth via direct contact with neurites in addition to secreting factors. The identification of cell surface molecules on SCs that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury.