Abstract
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 decrease of traction force of OEC with lower migratory capacity over myelin, 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.
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The authors thank R. Rycroft for linguistic advice and G. Tormen for technical assistance. This work was supported by FP7-PRIORITY, the MICINN (BFU2009-10848) and grants from the Instituto Carlos III (PI11/03028) and SGR2009-366 (Generalitat of Catalunya) to JADR. SN and PC were supported by the MICINN. DR is supported by a fellowship from the National Commission for Science and Technology (CONICYT, Chile). AB is a Sara Borrell postdoctoral research of the Instituto Carlos III. XT acknowledges support of the Spanish Ministry for Science and Innovation (BFU2009-07595) and the European Research Council (Grant Agreement 242993). F. Wandosell was supported by MICINN (SAF2009-12249-C02-01).
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S. Nocentini and D. Reginensi contribute equally to this study.
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Fig. S1. Myelin treatment activates RhoA and induces ERK1-2 phosphorylation in TEG3 cells. Time course of RhoA activation (a) and ERK1-2 phosphorylation (b) in TEG3 cells after myelin treatment. See the sections Materials and methods and Results for details (TIFF 2036 kb)
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Nocentini, S., Reginensi, D., Garcia, S. et al. Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell tracking and traction force microscopy. Cell. Mol. Life Sci. 69, 1689–1703 (2012). https://doi.org/10.1007/s00018-011-0893-1
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DOI: https://doi.org/10.1007/s00018-011-0893-1