Abstract
As olfactory receptor axons grow from the peripheral to the central nervous system (CNS) aided by olfactory ensheathing cells (OECs), the transplantation of OECs has been suggested as a plausible therapy for spinal cord lesions. The problem with this hypothesis is that OECs do not represent a single homogeneous entity, but, instead, a functionally heterogeneous population that exhibits a variety of responses, including adhesion and repulsion during cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. In this paper, we report a system based on modified OECs carrying magnetic nanoparticles as a proof of concept experiment enabling specific studies aimed at exploring the potential of OECs in the treatment of spinal cord injuries. Our studies have confirmed that magnetized OECs (i) survive well without exhibiting stress-associated cellular responses; (ii) in vitro, their migration can be modulated by magnetic fields; and (iii) their transplantation in organotypic slices of spinal cord and peripheral nerve showed positive integration in the model. Altogether, these findings indicate the therapeutic potential of magnetized OECs for CNS injuries.
Highlights
The elongation of newly generated olfactory receptor axons in the adult from the olfactory mucosa towards the central nervous system (CNS) is attributed to the supporting properties of olfactory ensheating cells (OECs), which ensheath and guide these axons [1,2]
Cell viability of M-olfactory ensheathing cells (OECs) was tested in both a time- and dose-dependent manner by using propidium iodide (PI) dye exclusion assay
At the highest concentration tested (25 μg/mL), the viability was found ~94.25% ± 3.12%, and not far from the control (~97.02% ± 5.05%) (Figure 2f). These results were confirmed by PI staining via fluorescent microscopy (Figure 2a–e); cells treated with magnetic nanoparticles (MNPs) exhibited permeability to PI similar to the control, except for 25 μg/mL, where few red spots are noticeable
Summary
The elongation of newly generated olfactory receptor axons in the adult from the olfactory mucosa towards the central nervous system (CNS) is attributed to the supporting properties of olfactory ensheating cells (OECs), which ensheath and guide these axons [1,2] Given their axon growth-promoting properties, OECs (natural or modified) have been transplanted into the injured spinal cord to promote axonal regeneration and functional recovery [3,4,5,6,7,8]. Knowledge of the mechanisms involved in inhibiting OEC migration is useful in the development of appropriate therapeutic strategies It has already been established in rats that OECs labelled with magnetic nanoparticles (MNPs) can be tracked in vivo by MRI to determine their migration details in normal and injured spinal cords, including the possibility that OECs can cross a complete spinal cord injury zone [24]. The use of MNP has been established for many clinical diagnostic/therapeutic uses, e.g., MRI contrast agents in magnetic resonance imaging [25], for cell tracking via MRI [26], magnetic hyperthermia [27], gene therapy [28], vectors for drug delivery [29], etc
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