Li, Y., Li, D. & Raisman, G. Interaction of olfactory ensheathing cells with astrocytes may be the key to repair of tract injuries in the spinal ord: the 'pathway hypothesis'. J. Neurocytol. 34, 343-351

Spinal Repair Unit, Institute of Neurology, UCL, Queen Square, London, WC1N 3BG, UK.
Journal of Neurocytology (Impact Factor: 1.94). 10/2005; 34(3-5):343-51. DOI: 10.1007/s11068-005-8361-1
Source: PubMed


Transplantation of cultured adult olfactory ensheathing cells has been shown to induce anatomical and functional repair of lesions of the adult rat spinal cord and spinal roots. Histological analysis of olfactory ensheathing cells, both in their normal location in the olfactory nerves and also after transplantation into spinal cord lesions, shows that they provide channels for the growth of regenerating nerve fibres. These channels have an outer, basal lamina-lined surface apposed by fibroblasts, and an inner, naked surface in contact with the nerve fibres. A crucial property of olfactory ensheathing cells, in which they differ from Schwann cells, is their superior ability to interact with astrocytes. When confronted with olfactory ensheathing cells the superficial astrocytic processes, which form the glial scar after lesions, change their configuration so that their outer pial surfaces are reflected in continuity with the outer surfaces of the olfactory ensheathing cells. The effect is to open a door into the central nervous system. We propose that this formation of a bridging pathway may be the crucial event by which transplanted olfactory ensheathing cells allow the innate growth capacity of severed adult axons to be translated into regeneration across a lesion so that functionally valuable connections can be established.

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Available from: Geoffrey Raisman, Apr 23, 2015
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    • "During the development of the olfactory pathway, cytoplasmic processes of OECs form conduits expressing cell adhesion and extracellular molecules, including Gal-1 (Puche et al. 1996; St John & Key, 1999; Vincent et al. 2005). The growth-promoting pathways created by OECs are thought to facilitate fasciculation and elongation of new axons towards their bulbar targets (Key & St John, 2002; Li et al. 2005a,b; Vincent et al. 2005). Cell surface carbohydrates on primary olfactory axons act as ligands for bivalent carbohydrate-binding proteins, such as Gal-1 (Puche & Key, 1996; Puche et al. 1996; St John & Key, 1999). "
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    ABSTRACT: Continuous lifelong neurogenesis is typical of the vertebrate olfactory system. The regenerative ability of olfactory receptor neurons is dependent on the glial cell type specific to the olfactory pathway, designated 'olfactory ensheathing cells'. Several studies to date have focused on mammalian olfactory ensheathing cells, owing to their potential roles in cell-based therapy for spinal cord injury repair. However, limited information is available regarding this glial cell type in non-mammalian vertebrates, particularly anamniotes. In the current immunocytochemical study, we analysed the features of olfactory ensheathing cells in the zebrafish, Danio rerio. Fish provide a good model for studying glial cells associated with the olfactory pathway of non-mammalian vertebrates. In particular, zebrafish has numerous valuable features that enable its use as a prime model organism for genetic, neurobiological and developmental studies, as well as toxicology and genomics research. Paraffin sections from decalcified heads of zebrafish were processed immunocytochemically to detect proteins used in the research on mammalian olfactory ensheathing cells, including glial fibrillary acid protein (GFAP), S100, neural cell adhesion molecule (NCAM), polysialylated NCAM (PSA-NCAM), vimentin (VIM), p75NTR and galactin (Gal)-1. Notably, GFAP, S100, NCAM and Gal-1 were clearly observed, whereas no vimentin staining was detected. Weak immunostaining for PSA-NCAM and p75NTR was evident. Moreover the degree of marker expression was not uniform in various tracts of the zebrafish olfactory pathway. The immunostaining patterns of the zebrafish olfactory system are distinct from those of other fish to some extent, suggesting interspecific differences. We also showed that the olfactory pathway of zebrafish expresses markers of mammalian olfactory ensheathing cells. The olfactory systems of vertebrates have similarities but there are also marked variations between them. The issue of whether regional and interspecific differences in immunostaining patterns of olfactory pathway markers have functional significance requires further investigation.
    Full-text · Article · Feb 2014 · Journal of Anatomy
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    • "SCs appeared to produce basement membrane, while OEG are capable of producing these molecules but not in the quantity seen in SCs grafted animals; rather, they may have induced other cells to produce extracellular matrix such as astrocytes or endothelial cells. This is not surprising given the role the OEG play in the olfactory system, where OEG form channels which stay present even after axonal degeneration in the olfactory bulb for axons to grow through and out to innervate areas of the olfactory bulb [83,84]. One mechanism for OEG reparative outcomes in the CNS is their close “cross-talking” with fibroblasts/meningeal cells [see [48,81] and ability to interact with these cells [9,85]. "
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    ABSTRACT: It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistical significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant tissue sparing was observed at both time points following glial SCs transplantation. In addition, OEG transplants showed significantly decreased chondroitin proteoglycan synthesis in the lesion site, suggesting a more CNS tolerant graft. These results show that transplantation of OEG and SCs in a sub-acute phase can improve anatomical outcomes after a contusion injury to the spinal cord, by increasing the number of spared/regenerated supraspinal fibers, reducing cavitation and enhancing tissue integrity. This provides important information on the time window of glial transplantation for the repair of the spinal cord.
    Full-text · Article · Sep 2013 · BMC Neuroscience
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    • "which in turn lead to the loss of axonal connections [27] [28] [29] [30] [31] [32] [33] [34]. Hence, according to the above mentioned reasons, regeneration and recovery of damaged CNS may be much more difficult than PNS. "
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    ABSTRACT: As the field of nerve tissue engineering advances, new biomaterials and structures are required to improve the regeneration of damaged nerves. Carbon nanostructures have been recognized as potential candidates to develop neural prostheses due to their one-dimensional nanostructures and similar nanoscale dimensions to neuritis as well as their unique electrical and mechanical properties when being used as a scaffold. This review addresses the promising application of carbon nanostructures in the repair of injured nerves. As a new viewpoint, the possibility of utilizing carbon nanostructures to repair a long gap in a severed nerve will be discussed as well.
    Full-text · Article · Apr 2012 · Ceramics International
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