Intravenously transplanted human neural stem cells migrate to the injured spinal cord in adult mice in an SDF-1- and HGF-dependent manner

Abstract

Neural stem cell (NSC) transplantation has exhibited considerable therapeutic potential in spinal cord injury. However, most experiments in animals have been performed by injecting these cells directly into the injured spinal cord. A cardinal feature of NSCs is their exceptional migratory ability through the nervous system. Based on the migratory ability of NSCs, we investigated whether minimally invasive intravenous delivery of NSCs could facilitate their migration to the injured spinal cord and identified the chemo-attractants secreted by the lesions. Nude mice were injected intravenously with labelled human NSCs at 3, 7 and 10 days after the compression of the spinal cord at the T8 level. The migration of NSCs to the lesioned spinal cord was highest at 7 days after injury; this correlated with the peak of hepatocyte growth factor and stromal cell-derived factor-1 mRNA expressions in the lesion but not with the disruption of the blood-brain barrier. Finally, the grafted NSCs differentiated into neuronal and glial subpopulations at 21 days after transplantation. Our study suggests that intravenously administered NSCs can be employed as a renewable source for replacing lost cells for the treatment of spinal cord injuries.