Human endothelial cells secrete neurotropic factors to direct axonal growth of peripheral nerves

Understanding how nerves spontaneously innervate tissues or regenerate small injuries is critical to enhance material-based interventions to regenerate large scale, traumatic injuries. During embryogenesis, neural and vascular tissues form interconnected, complex networks as a result of signaling between these tissue types. Here, we report that human endothelial cells (HUVECs) secrete brain-derived neurotrophic factor (BDNF), which significantly stimulated axonal growth from chicken or rat dorsal root ganglia (DRGs). HUVEC-conditioned medium was sufficient to enhance axonal growth, demonstrating that direct cell-cell contact was not required. When BDNF was neutralized, there was a significant reduction in axonal growth when incubated in HUVEC-conditioned medium and in direct co-culture with HUVECs. These data show that HUVECs secrete neurotrophic factors that significantly enhance axonal growth, and can inform future in vivo studies to direct or pattern the angiogenic response in regenerating tissues to encourage re-innervation.