Neurotrophic properties of olfactory ensheathing glia (original) (raw)
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Neuroscience letters, 2009
Olfactory ensheathing cells (OECs) are specialized glial cells that guide olfactory receptor axons from the nasal mucosa into the brain where they make synaptic contacts in the olfactory bulb. While a number of studies have demonstrated that in vivo transplantation of OECs into injured spinal cord results in improved functional outcome, precise cellular mechanisms underlying this improvement are not fully understood. Current thinking is that OECs can encourage axonal regeneration, provide trophic support for injured neurons and for angiogenesis, and remyelinate axons. However, Schwann cell (SC) transplantation also results in significant functional improvement in animal models of spinal cord injury. In culture SCs and OECs share a number of phenotypic properties such as expression of the low affinity NGF receptor (p75). An important area of research has been to distinguish potential differences in the in vivo behavior of OECs and SCs to determine if one cell type may offer greater a...
Olfactory Ensheathing Glia: Drivers of Axonal Regeneration in the Central Nervous System?
Journal of Biomedicine and Biotechnology, 2002
Olfactory ensheathing glia (OEG) accompany olfactory growing axons in their entry to the adult mammalian central nervous system (CNS). Due to this special characteristic, considerable attention has been focused on the possibility of using OEG for CNS regeneration. OEG present a large heterogeneity in culture with respect to their cellular morphology and expressed molecules. The specific characteristics of OEG responsible for their regenerative properties have to be defined. These properties probably result from the combination of several factors: molecular composition of the membrane (expressing adhesion molecules as PSA-NCAM, L1 and/or others) combined with their ability to reduce glial scarring and to accompany new growing axons into the host CNS. Their capacity to produce some neurotrophic factors might also account for their ability to produce CNS regeneration.
Axonal signalling and the making of olfactory ensheathing cells: a hypothesis
Neuron Glia Biology, 2006
Olfactory ensheathing cells (OECs) are Schwann cell-like glial cells of the olfactory system that promote neural repair under experimental conditions. It is a matter of debate in how far OECs resemble Schwann cells and whether they possess specific properties. Although OECs have been characterized mainly with respect to their regenerative effects after transplantation, both their cellular identity and the regulating factors involved have remained vague. The aim of this article is to define OEC and Schwann-cell identity in molecular terms, and to discuss crucial factors that are involved in determination in vitro and in vivo. Distinct OEC features such as the down-regulation of the low affinity neurotrophin receptor p75NTR by neuronal contact are apparent in vivo under physiological conditions, whereas OECs acquire a Schwann cell-like phenotype and up-regulate p75NTR expression in vitro and following transplantation into the lesioned spinal cord. This might indicate that establishmen...
Molecular Brain Research, 2001
In the primary olfactory pathway axons of olfactory neurons (ONs) are accompanied by ensheathing cells (ECs) as the fibres course towards the olfactory bulb. Ensheathing cells are thought to play an important role in promoting and guiding olfactory axons to their appropriate target. In recent years, studies have shown that transplants of ECs into lesions in the central nervous system (CNS) are able to stimulate the growth ofaxons and in some cases restore functional connections. In an attempt to identify a possible mechanism underlying EC support for olfactory nerve growth and CNS axonal regeneration, this study investigated the production of growth factors and expression of corresponding receptors by these cells. Three techniques immunohistochemistry, enzyme linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess growth factor expression in cultured ECs. Immunohistochemistry showed that ECs expressed nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF). ELISA confirmed the intracellular presence of NGF and BDNF and showed that, compared to BDNF, about seven times as much NGF was secreted by ECs. RT-PCR analysis demonstrated expression of mRNA for NGF, BDNF, GDNF and neurturin (NTN). In addition, ECs also expressed the receptors trkB, GFRa-1 and GFRa-2. The results of the experiments show that ECs express a number of growth factors and that BDNF in particular could act both in a paracrine and autocrine manner.
Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury
Journal of Rehabilitation Research and Development, 2008
Contusive spinal cord injury (SCI) results in a complex lesion that includes cellular and axonal loss, microglia and macrophage activation, and demyelination. These changes result in permanent neurological deficits in people with SCI and in high financial costs to society. Unlike the peripheral nervous system (PNS), in which axonal regeneration can occur, axonal regeneration in the central nervous system (CNS) is extremely limited. This limited regeneration is thought to result from a lack of a permissive environment and from active inhibitory molecules that are present in the CNS but minimal in the PNS. Currently, cell transplantation approaches are among several experimental strategies being investigated for the treatment of SCI. In the olfactory system, a specialized glial cell called the olfactory ensheathing cell (OEC) has been shown to improve functional outcome when transplanted into rodents with SCI, and clinical studies transplanting OECs into patients with SCI are ongoing in China, Portugal, and other sites. Yet, a number of controversial issues related to OEC biology and transplantation must be addressed to understand the rationale and expectations for OEC cell therapy approaches in SCI. This review provides information on these issues for spinal cord medicine clinicians.
European Journal of Neuroscience, 2008
Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration‐associated genes. Cell body treatment with brain‐derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration‐associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a c...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998
The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional impairment. To induce axonal regeneration in the transected adult rat spinal cord, we have used the axonal growth-promoting properties of adult olfactory bulb ensheathing glia (EG). Schwann cell (SC)-filled guidance channels were grafted to bridge both cord stumps, and suspensions of pure (98%) Hoechst-labeled EG were stereotaxically injected into the midline of both stumps, 1 mm from the edges of the channel. In EG-transplanted animals, numerous neurofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-, and serotonin-immunoreactive fibers traversed the glial scars formed at both cord-graft interfaces. Supraspinal serotonergic axons crossed the transection gap through connective tissue bridges formed on the exterior of the channels, avoiding the channel interior. Strikingly, after crossing the distal glial scar, these fibers elongated in white and periaqueductal gray ...