Peripherally–derived olfactory ensheathing cells do not promote primary afferent regeneration following dorsal root injury

Abstract

Olfactory ensheathing cells (OECs) may support axonal regrowth, and thus might be a viable treatment for spinal cord injury (SCI); however, peripherally-derived OECs remain untested in most animal models of SCI. We have transplanted OECs from the lamina propria (LP) of mice expressing green fluorescent protein (GFP) in all cell types into immunosuppressed rats with cervical or lumbar dorsal root injuries. LP-OECs were deposited into either the dorsal root ganglion (DRG), intact or injured dorsal roots, or the dorsal columns via the dorsal root entry zone (DREZ). LP-OECs injected into the DRG or dorsal root migrated centripetally, and migration was more extensive in the injured root than in the intact root. These peripherally deposited OECs migrated within the PNS but did not cross the DREZ; similarly, large- or small-caliber primary afferents were not seen to regenerate across the DREZ. LP-OEC deposition into the dorsal columns via the DREZ resulted in a laminin-rich injection track: due to the pipette trajectory, this track pierced the glia limitans at the DREZ. OECs migrated centrifugally through this track, but did not traverse the DREZ; axons entered the spinal cord via this track, but were not seen to reenter CNS tissue. We found a preferential association between CGRP-positive small- to medium-diameter afferents and OEC deposits in injured dorsal roots as well as within the spinal cord. In the cord, OEC deposition resulted in increased angiogenesis and altered astrocyte alignment. These data are the first to demonstrate interactions between sensory axons and peripherally-derived OECs following dorsal root injury.

Calcitonin gene-related peptide immunoreactivity in chronic human spinal cord injury

“…A computerized program provided average density measurements for each 20-mm segment of the 720-mm long rectangular strip. To quantify CGRP-positive axon density in the spinal cord, we carried an automated thresholding procedure, 31,33,34 which first defines the thickest and brightest regions, and then, following application of a Laplacian omnidirectional edge-detection filter, the finer processes ( Figure 1, bottom). The edge-detection filter effectively normalizes the signal-to-noise ratio such that small variations in immunoreactivity across sections are eliminated.…”

SPARC from Olfactory Ensheathing Cells Stimulates Schwann Cells to Promote Neurite Outgrowth and Enhances Spinal Cord Repair

“…Crush of the dorsolateral funiculus was performed as described previously (Ramer et al, 2004a;Richter et al, 2005). In summary, animals were anesthetized with xylazine/ketamine (10 mg/kg, i.p.…”

“…Many OEC transplant studies have produced conflicting data regarding the ability of OECs to promote regeneration, even in the same model of SCI (Ramon-Cueto and Nieto-Sampedro, 1994;Ramer et al, 2004a;Riddell et al, 2004). Some of these differences may be attributable to different culture conditions that could change the biology of OECs and how they behave after transplantation (Franklin et al, 1996;Li et al, 1997;RamonCueto et al, 1998;Ramer et al, 2004b).…”

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…[227][228][229] However, recent data from our group and others indicate that OEC transplantation does not support regeneration of sensory axons across the injured DREZ. [230][231][232] Using OECs from the GFP mouse, we have observed that OEC injection into the spinal cord mechanically disrupts the DREZ, permitting sensory axon ingrowth but not functional regeneration involving the re-acquisition of appropriate targets on the other side of the injured DREZ. 232 After SCI, OECs were also applied to remodel a PNS-CNS interface, namely, that established by grafting Schwann cells into CNS tissue.…”

“…[230][231][232] Using OECs from the GFP mouse, we have observed that OEC injection into the spinal cord mechanically disrupts the DREZ, permitting sensory axon ingrowth but not functional regeneration involving the re-acquisition of appropriate targets on the other side of the injured DREZ. 232 After SCI, OECs were also applied to remodel a PNS-CNS interface, namely, that established by grafting Schwann cells into CNS tissue. When OECs were injected into the proximal and distal stumps of transected spinal cord spanning a SC bridge, regenerating axons crossed the graft-host interfaces and reentered the spinal cord.…”