Remyelination by transplanted olfactory ensheathing cells

Abstract

The olfactory ensheathing cells (OECs) of the peripheral olfactory system associate with the axons of the first cranial nerve. These axons are not myelinated by OECs because of their very small diameter. However, when OECs are transplanted into areas where they encounter larger-diameter axons, such as in a model of primary demyelination, these cells assume a myelinating phenotype. Myelinating OECs very closely resemble myelinating Schwann cells by all criteria currently examined, including morphology, ultrastructure, biochemistry, and transcriptional regulation. Indeed, it is currently impossible to reliably distinguish myelinating OECs and myelinating Schwann cells that have been transplanted into experimental models of CNS demyelination. This article describes recent studies on the myelinating properties of transplanted OECs, focusing on their intrinsic myelinating potential and how this can be augmented by the presence of meningeal cells. The relative merits of OECs compared with Schwann cells when transplanted into astrocyte-containing lesions in the CNS are discussed together with their potential role in transplanted-mediated repair of demyelinating disease such as multiple sclerosis.

Neural crest origin of olfactory ensheathing glia

“…This finding explains the similarities between OECs and Schwann cells (3,(9)(10)(11) and raises interesting questions about the control of NCC differentiation into OECs versus Schwann cells. It is also potentially of high clinical significance.…”

“…All other peripheral glia, i.e., myelinating and nonmyelinating Schwann cells in peripheral nerves, and satellite cells in peripheral ganglia are derived from neural crest cells (NCCs) (8), which emigrate from the dorsal neural tube early in development. OECs are similar in many ways to immature and nonmyelinating Schwann cells (3,(9)(10)(11), ensheathing bundles of small-diameter axons without forming myelin (Fig. S1A); furthermore, the OEC transcriptome is closer to that of Schwann cells than astrocytes (12), and OECs will myelinate larger-diameter axons indistinguishably from Schwann cells, both in vitro and after transplantation into demyelinated spinal cord lesions (9-11, 13, 14).…”

Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC

“…When transplanted into a damaged region of the central nervous system OECs can remyelinate, guide and support axons (35,36). They also mediate their effects through the provision of growth factors that encourage plasticity, stimulate angiogenesis, interact with the glial scar and are involved in immune modulation (For a review, see 37,38).…”

Embryonic Neural Stem Cell Differentiation to Aldynoglia Induced by Olfactory Bulb Ensheathing Cell-Conditioned Medium

“…In contrast, the peripheral nervous system environment is supportive of regeneration because Schwann cells provide suitable substrates for regrowing axons (Hirsch & Bähr, 1999;Lavdas et al, 2008). Knowledge of the mechanisms that direct stem cell differentiation to diverse cell phenotypes raises the possibility of generating in vitro a large population of cells of specific phenotypic characteristics that can be used to promote regeneration after a CNS injury by means of autologous transplantation from previously differentiated precursor cells (Franklin, 2003), in our case this particular phenotype is represented by the aldynoglia, which can be obtained by inducing MNP cells to differentiate using OBEC-conditioned medium. It would also be feasible to attempt to generate new cells endogenously by activating specific signalling pathways that elicit the production of regeneration-promoting glial cells (Kulbatski et al, 2008) of the aldynoglia phenotype.…”