Olfactory ensheathing cells proliferate from local OECs and from precursors in the olfactory mucosa after different type of injuries

Olfactory ensheathing cells (OECs) support the regeneration of olfactory sensory neurons throughout life. However, it remains unclear how OECs respond to a major injury and whether OEC precursors within the olfactory mucosa give rise to new OECs in those conditions. We examined the proliferation and migration of OECs in two postnatal animal models of olfactory axon degeneration. In the first model, we surgically removed an olfactory bulb including the nerve fibre layer which contains OECs. In the second model, intraperitoneal injection of methimazole was used to selectively destroy the entire olfactory epithelium while not directly affecting OECs. Proliferating cells were labelled by the thymidine analogue, ethynyl deoxyuridine (EdU). In the unilateral bulbectomy model, there was a large stimulation of OEC proliferation throughout the olfactory nerve up to 14 days after bulbectomy. Using a pulse-chase EdU application, we tracked cells that had proliferated and found that OEC precursors lining the basal layer of the olfactory epithelium also gave rise to OECs that subsequently migrated along the length of the olfactory nerve. In the methimazole model, a small but significant proliferation of OECs was induced 7-10 days after axon death, with proliferation occurring in all regions of the olfactory nerve. These results demonstrate that OECs actively respond to widespread degeneration of olfactory axons and that OECs arise from both local proliferation as well as from OEC precursors. These results have important implications for selecting the source of OECs for neural regeneration therapies.