Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy

Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but, instead, a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo Receptor complex and that their migration is blocked by Myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over Myelin. Our data relate the absence of traction force of OEC with lower migratory capacity, which correlates with changes in the F-Actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo Receptor inhibitor NEP1-40

The Migration of Olfactory Ensheathing Cells during Development and Regeneration

The primary olfactory nervous system is unique in that it continuously renews itself and regenerates after injury. These properties are attributed to the presence of olfactory glia, termed olfactory ensheathing cells (OECs). Evidence is now emerging that individual OEC populations exist with distinct anatomical localisations and physiological properties, but their differential roles have not been determined. Unlike other glia, OECs can migrate from the periphery into the central nervous system, and organised OEC migration can enhance axonal extension after injury. Despite this, the mechanisms regulating OEC migration are largely unknown. Here, we provide an overview of the roles of OECs in development and adulthood. We review the latest research describing the differences between individual OEC subpopulations and discuss potential regulatory mechanisms for OEC guidance and migration. Using advanced time-lapse techniques, we have obtained novel insights into how OECs behave in a complex multicellular environment which we discuss here with particular focus on cell-cell interactions. Significantly, transplantation of OECs constitutes a promising novel therapy for nerve injuries, but results are highly variable and the method needs improvement. We here review the roles of transplanted OECs in neural repair of damaged neuronal tracts distinct from the primary olfactory nervous system.Griffith Sciences, Griffith Institute for Drug DiscoveryFull Tex

Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions

The growth and guidance of primary olfactory axons are partly attributed to the presence of olfactory ensheathing cells (OECs). However, little is understood about the differences between the subpopulations of OECs and what regulates their interactions. We used OEC-axon assays and determined that axons respond differently to peripheral and central OECs. We then further purified OECs from anatomically distinct regions of the olfactory bulb. Cell behaviour assays revealed that OECs from the olfactory bulb were a functionally heterogeneous population with distinct differences which is consistent with their proposed roles in vivo. We found that the heterogeneity was regulated by motile lamellipodial waves along the shaft of the OECs and that inhibition of lamellipodial wave activity via Mek1 abolished the ability of the cells to distinguish between each other. These results demonstrate that OECs from the olfactory bulb are a heterogeneous population that use lamellipodial waves to regulate cell-cell recognition