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Behaviour and effects of peripheral olfactory ensheathing cells transplanted at the site of acute spinal cord injury Ramer, Leanne Margaret

Abstract

Mammalian olfactory neurons are replenished from a progenitor pool in the PNS and extend axons into the CNS throughout adult life. This capacity for neurits outgrowth has been attributed in part to olfactory ensheathing cells (OECs), glia that fasciculate olfactory axons in both the PNS and the CNS. When transplanted at or near the site of spinal cord injury (SCI) in rodents, OECs from the olfactory bulb of rodents and humans have elicited regeneration and remyelination of damaged axons, sometimes with concomitant functional recovery. As a result, OECs have emerged as candidates for autologous transplantation to repair human SCI, and Phase I clinical trials are underway. OECs from the olfactory bulb have been isolated and examined in culture and after transplantation into animal SCI for more than a decade; however, their behaviour upon transplantation remains ambiguous, as they lack a defining molecular marker, and the mechanism of OEC-mediated repair of SCI remains debatable. More pertinent to the use of OECs in the clinic is the dearth of experiments testing the efficacy of OECs derived from the lamina propria (LP-OECs), the source of OECs for clinical autotransplantation. Here, LP-OECs were purified from GFP-expressing mice and transplanted at the site of acute dorsolateral funiculus crush in immunosuppressed rats and mice; spinal cords were examined histologically at 48h, 7d, 28d and 60d (rats) and 28 d (mice). LP-OECs had limited survival and migration in both rats and mice: after 28d, LP-OECs were confined to the lesion site in both species, and no LP-OECs were encountered in rat spinal cords after 60d. However, LP-OECs prevented cavitation and altered astrogliosis: after 28d, the lesion sites of LP-OEC transplanted animals contained many axons, as well as Schwann cells and new blood vessels, both of which might provide a scaffold for axonal growth. Serotonergic and noradrenergic bulbospinal axons exhibited robust sprouting, with a few axons regenerating across the lesion site; anterogradely-labeled rubrospinal axons did not regenerate. Thus, despite a transient presence and limited migration within host spinal tissue, LP-OECs have beneficial effects at the site of acute rodent SCI, and support growth of some supraspinal axons.

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