Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury

Abstract

Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.