Peripherally-derived olfactory ensheathing cells do not promote primary afferent regeneration following dorsal root injury.
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.
Ramer
Leanne M
LM
International Collaboration on Repair Discoveries (ICORD), Vancouver, British Columbia, Canada. leanne@icord.org
Richter
Miranda W
MW
Roskams
A Jane
AJ
Tetzlaff
Wolfram
W
Ramer
Matt S
MS
D000344:Afferent Pathways / Q000254:growth & development* / Q000293:injuries / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D003714:Denervation; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000254:growth & development / Q000473:pathology / Q000601:surgery; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism; D008164:Luminescent Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology; D009416:Nerve Regeneration; D009457:Neuroglia / Q000166:cytology / Q000637:transplantation*; D009831:Olfactory Mucosa / Q000166:cytology / Q000254:growth & development / Q000637:transplantation*; D011843:Radiculopathy / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D019051:Rhizotomy; D013116:Spinal Cord / Q000254:growth & development / Q000473:pathology / Q000601:surgery; D013126:Spinal Nerve Roots / Q000254:growth & development / Q000293:injuries* / Q000473:pathology; D016378:Tissue Transplantation / Q000379:methods; D014183:Transplantation, Heterologous; D017211:Treatment Failure
D007797:Laminin; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D015740:Calcitonin Gene-Related Peptide