Lamina propria and olfactory bulb ensheathing cells exhibit differential integration and migration and promote differential axon sprouting in the lesioned spinal cord.
Olfactory bulb-derived (central) ensheathing cell (OB OEC) transplants have shown significant promise in rat models of spinal cord injury, prompting the use of lamina propria-derived (peripheral) olfactory ensheathing cells (LP OECs) in both experimental and clinical trials. Although derived from a common embryonic precursor, both sources of OECs reside in different nervous system compartments postnatally, and their ability to promote regeneration and efficacy after transplantation may differ depending on both their source and mode of transplantation. Here, we have purified green fluorescent protein-expressing LP and OB OECs, assayed their biological differences in vitro, and transplanted them acutely either directly into or rostral and caudal to a dorsolateral funiculus crush. LP and OB OECs exhibit multiple morphological and antigenic similarities in vitro, and, after transplantation, they both attenuate lesion and cavity formation and promote angiogenesis, endogenous Schwann cell infiltration, and axonal sprouting. However, an increased mitotic rate and migratory ability of LP OECs in vitro was reflected in vivo by their superior ability to migrate within the spinal cord, reduce cavity formation and lesion size, and differentially stimulate outgrowth of axonal subpopulations compared with OB OECs. An undesired behavior (autotomy) was also significantly enhanced by LP OEC, over OB OEC, transplantation. These results suggest that LP and OB OECs exhibit intrinsic biological differences that, after transplantation into the lesioned CNS, result in differences in postlesion spinal cord neuropathology and anatomical and behavioral regeneration outcomes that also vary depending on direct versus rostrocaudal transplantation.
Richter
Miranda W
MW
Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
Fletcher
Patrick A
PA
Liu
Jie
J
Tetzlaff
Wolfram
W
Roskams
A Jane
AJ
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000637:transplantation; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D017690:Cell Transplantation / Q000379:methods / Q000502:physiology; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D009416:Nerve Regeneration / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D009831:Olfactory Mucosa / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000473:pathology / Q000601:surgery*