Olfactory ensheathing cells facilitate neurite sprouting and outgrowth by secreting high levels of hevin.

Transplantation of olfactory ensheathing cells (OECs) has been shown to enhance synapse formation. However, the mechanisms underlying this effect are not completely understood. We performed profiling of the OEC and astrocyte secretomes via a proteomics approach, in case hevin secreted by astrocytes might be involved in the formation of synapses. Semi-quantitative proteomic analysis revealed that 25 proteins were highly expressed, and 22 were weakly expressed in OEC conditioned medium compared with astrocyte conditioned medium. These molecules are highly associated with neural differentiation and regeneration, enzyme regulatory activity, and growth factor binding. The quantification data of clusterin, fibronectin, hevin, insulin-like growth factor binding protein 2 and secreted protein acidic and rich in cysteine were further confirmed by western blotting. Moreover, the addition of hevin in the culture medium improved neurite sprouting and outgrowth of differentiated neural stem cells. The greater expression of hevin in OEC conditioned medium than in astrocyte conditioned medium was associated with a greater capacity of synaptic formation. Thus, our results indicate that soluble factors secreted by OECs provide a permissive environment for nerve repair, and hevin is one of the key molecules facilitating neurite sprouting and outgrowth.