Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury

Abstract

Olfactory ensheathing cells (OECs) have been reported to migrate long distances and to bridge lesion sites, guiding axonal regeneration after spinal cord injury (SCI). To understand mechanisms of OEC migration and axonal guidance, we injected lamina propria OECs 1 mm rostral and caudal to C4 SCI sites. One month later, OECs formed an apparent migrating cell tract continuously extending from the injection site through the lesion, physically bridging the lesion. Confocal immunolabeling demonstrated that, whereas this cell tract displaced host astrocytes, descending or ascending long tract axons did not preferentially extend into the cell tract and OECs failed to support bridging of corticospinal axons. Notably, the "bridging" tract of OECs formed within 1 h of cell injection, raising the possibility that cells passively spread from the pressure injection site rather than actively migrating. Control injections of bone marrow stromal cells (MSCs) or fibroblasts 1 mm from the lesion site also rapidly dispersed into the lesion cavity. Cell tracts extending into the lesion site were not seen when cells were injected either at low volumes, into spinal cord gray matter, or 3 d before or 9 d after SCI. OECs proliferated in injection sites, cell tracts, and lesion sites, indicating that OECs can also accumulate through cell proliferation. Thus, OECs do not appear to exhibit significant migratory properties when grafted to the spinal cord, exhibit no detectable difference in promoting axon growth into a SCI site compared with MSCs or fibroblasts, and do not support bridging of corticospinal axons beyond a dorsal column lesion.

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

“…If nogo neutralization influences axonal growth, a more likely mechanism of action may be enhanced sprouting of spared projections (41). Similarly, reports that olfactory ensheathing cells promote corticospinal tract regeneration are the subject of uncertainty (42,43).…”

Increased migration of olfactory ensheathing cells secreting the Nogo receptor ectodomain over inhibitory substrates and lesioned spinal cord

“…The migratory potential of OECs is crucial to their function [16]. However, studies of the migration capacity and behaviour of OECs after transplantation in SCI models have led to contradictory results [17][18][19]. Nevertheless, it has been demonstrated that in injured spinal cord, rat and human OECs migrate for shorter distances, in both rostral and caudal directions, compared to non-injured spinal cords [20].…”

Potential of olfactory ensheathing cells for cell-based therapy in spinal cord injury

“…We should point out that in one study, functional improvement was not observed following OEC transplantation but was observed following Schwann cell transplantation [64]. Moreover, other investigators have not found unique migratory properties of OECs [65] and one report questioned the efficacy of transplantation of lamina propria into complete spinal cord transection [66].…”