Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6017585 | Experimental Neurology | 2014 | 16 Pages |
Abstract
Olfactory ensheathing glial cells (OECs) are a specialized type of glia that form a continuously aligned cellular pathway that actively supports unprecedented regeneration of primary olfactory axons from the periphery into the central nervous system. Implantation of OECs stimulates neural repair in experimental models of spinal cord, brain and peripheral nerve injury and delays disease progression in animal models for neurodegenerative diseases like amyotrophic lateral sclerosis. OECs implanted in the injured spinal cord display a plethora of pro-regenerative effects; they promote axonal regeneration, reorganize the glial scar, remyelinate axons, stimulate blood vessel formation, have phagocytic properties and modulate the immune response. Recently genome wide transcriptional profiling and proteomics analysis combined with classical or larger scale “medium-throughput” bioassays have provided novel insights into the molecular mechanism that endow OECs with their pro-regenerative properties. Here we review these studies and show that the gaps that existed in our understanding of the molecular basis of the reparative properties of OECs are narrowing. OECs express functionally connected sets of genes that can be linked to at least 10 distinct processes directly relevant to neural repair. The data indicate that OECs exhibit a range of synergistic cellular activities, including active and passive stimulation of axon regeneration (by secretion of growth factors, axon guidance molecules and basement membrane components) and critical aspects of tissue repair (by structural remodeling and support, modulation of the immune system, enhancement of neurotrophic and antigenic stimuli and by metabolizing toxic macromolecules). Future experimentation will have to further explore the newly acquired knowledge to enhance the therapeutic potential of OECs.
Keywords
EGFRGFAPMBPCOX-2N-cadherinRhoACNTFAPPNGFGDNFPAMPFGF2GBATGFcyclo-oxygenase-2P2XIL6L1CAMSmad7TIMP2P2YNFkBLPLNRP1MMP2CX3CL1PAR1S100SERPINE1Cyr61SPARCFZD1TNFRSF1ACDH2NCAM1Vav1Angpt2NEFLSCARB2GFRA1ADAMTS1TNFTHBDbeta-glucocerebrosidaseMSLNNT4/5LEPRE1cell adhesion molecule L1NID2arabinosylcytosineONFras homolog family member ABDNFAdenosine TriphosphateATPAra-CSemaangiopoietin 2pathogen-associated molecular patterngrowth-regulated oncogeneinterleukin-6Axon regenerationClinicalBioinformaticstransforming growth factorThrombomodulinTissue repairNeural repairtumor necrosis factor alphatyrosine hydroxylaseSemaphorinScreenepidermal growth factorfibroblast growth factor 2brain derived neurotrophic factorOlfactory nerveVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)nerve growth factorglial-derived neurotrophic factornuclear factor kappaBfractalkineTissue-type plasminogen activatorLipoprotein lipasematrix metalloproteinase 2MesothelinPlasminogen activator inhibitor-1Molecular mechanismsRaramapNeurotrophin 4/5neuropilin 1Glial fibrillary acidic proteinmicrotubule-associated proteinMyelin basic proteinamyloid beta precursor proteinRho-associated protein kinaseTransplantationFunctional genomicsgalactosylceramidaseGroleukemia inhibitory factor receptorlow affinity nerve growth factor receptorCiliary neurotrophic factor receptorRock
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Authors
Kasper C.D. Roet, Joost Verhaagen,