Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM‐dependent mechanism

Abstract

Olfactory ensheathing cells (OECs) support the ability of the olfactory neuraxis to continually retarget within the mature central nervous system. This has led many groups to transplant OECS into the lesioned rodent spinal cord (SCd) in vivo, with variable degrees of anatomical, physiological, and behavioral success. Some of the most conflicting results in OEC transplantation have come from the corticospinal tract (CST) which has shown a relatively poor regeneration response. Although spinal neurite sprouting occurs in response to OECs in vivo and in vitro, we do not know if OECs possess the molecular machinery to stimulate outgrowth of functionally important motor tracts like the CST. Here, we assay cultured postnatal day 8 mouse CST neurons expressing yellow fluorescent protein (YFP) for their ability to extend axons and dendrites in response to different glia, and show that CST axons elongate in response to proteins in OEC plasma membrane (PM). In contrast, CST dendritic branching preferentially occurs in response to factors secreted by both OECs and astrocytes. We identify the L1-neural cell adhesion molecule (L1-NCAM) as a major component of OEC-induced corticospinal axon elongation, and have determined that OEC PM factors (including L1), can stimulate CST outgrowth even when inhibition is induced by myelin associated glycoprotein. Together, these results suggest that in the right context, OEC-derived PM factors could enhance CST axonal regeneration, and potentially contribute to approaches to ameliorate recovery from SCd injury.

Olfactory mucosa: a rich source of cell therapy for central nervous system repair

“…Studies in animals isolating OECs from the OB proved that OECs can promote axonal outgrowth (Witheford et al, 2013) and benefit in several animal models of CNS traumatic injuries . We have previously demonstrated that OEC-conditioned medium can induce NSCs differentiated into neurons (Duan et al, 2011).…”

Therapeutic Potential of Olfactory Ensheathing Cells and Mesenchymal Stem Cells in Spinal Cord Injuries

“…The source of cells with regenerative potential should be discussed before the choice for particular therapy (classification based on the source of those cells is shown in Figure 2). This review is focused on therapies applying olfactory ensheathing cells, which are proved to act as stimulating axonal growth factors [14] and mesoderm derived mesenchymal stem cells (mainly derived from bone marrow) and their implantation in patients with SCI which are believed to occur through regulation of the immune system, leading to decreased cell death [15]. …”

Ginsenoside Rg1 Promotes the Migration of Olfactory Ensheathing Cells <i>via</i> the PI3K/Akt Pathway to Repair Rat Spinal Cord Injury

“…[25][26][27] NCAM1, which is a major component of OEC-induced corticospinal axon elongation, plays a key role in OEC migration. 28,29) The RT-PCR findings indicate that ginsenoside Rg1 increased the expression of MMP-2, MMP-9, and NCAM1 genes, which stimulate ginsenoside Rg1 in enhancing the migration characteristic of OECs. Thus, these current findings confirm our hypothesis that ginsenoside Rg1 promotes OEC migration and facilitates the repair of SCI via the inhibition of scar formation.…”