Intraspinal Transplantation of hNT Neurons in the Lesioned Adult Rat Spinal Cord

Abstract

Background: The role of neural transplantation as a restorative strategy for spinal cord injury continues to be intensely investigated. Ideally, the tissue source for transplantation must be readily available, free of disease and able to survive and mature following implantation into the adverse environment created by the injury. We have studied the use of a commercially available cell line of cultured human neurons (hNT neurons) as a tissue source for neural transplantation in spinal cord injury. Methods: Following a left lateral thoracic hemisection, 54 immunosuppressed, female Wistar rats were randomly allocated into different treatment groups; hemisection only or hemisection and hNT cell transplantation (via a bridge, double or triple graft). Grafting occurred three days after spinal cord injury. After thirteen weeks the animals were sacrificed and tissue sections were stained with human neuron specific enolase and human specific neural cell adhesion molecule. Results: Immunohistochemical evidence of graft survival was displayed in 66.7% of the surviving, grafted animals. Fibre outgrowth, greatest in the bridge and triple grafts, was observed in both rostral and caudal directions essentially bridging the lesion. Double grafts were smaller, displaying less fibre outgrowth, which did not cross the lesion. Long fibre outgrowth was evident up to 2 cm from the graft as assessed by tracing and immunohistochemical studies. Conclusions: Bridge and triple grafts displayed greater growth and enabled the hNT graft to essentially bridge the lesion. This suggests that hNT neurons have the potential to structurally reconnect the proximal and distal spinal cord across the region of injury.