Mechanisms of olfactory ensheathing cell-enhanced neurite outgrowth and axon regeneration after spinal cord injury
Olfactory ensheathing cells (OECs) provide a pro-regenerative environment for the axons of olfactory receptor neurons and therefore are a promising candidate for cell transplantation therapy following spinal cord injury. We previously showed that OEC transplantation supports axon regeneration and functional re-connectivity following complete spinal cord injury, yet lack of an OEC-specific marker limited our ability to determine how they promoted these beneficial effects. Using both in vitro and in vivo models, we investigated the mechanisms by which OECs mediate axon regeneration. OECs enhance neurite outgrowth of postnatal cortical neurons in a scar-like culture model. We provide strong evidence that direct OEC-neurite alignment is critical to enhance neurite outgrowth in scar-like astrocyte and meningeal fibroblast inhibitory environments. We also tested eGFP-OECs from transgenic rats and showed that they facilitate neurite outgrowth in vitro. Then in a short-term study, we analyzed OEC survival, migration, and distribution within the lesion site of complete spinal cord transected rats. We found that rats transplanted with OECs preserve and associate with axons and neurons in the lesion core, reduce the presence of inhibitory CSPGs and myelin debris, and reduce secondary tissue damage due to microglial and macrophage activation and infiltration post-injury. Collectively, these data support a neuroprotective and proregenerative role of OECs through the modulation of glial scar formation following a complete spinal cord transection.