ABSTRACT
BACKGROUND: Axonal regeneration is a prerequisite for recovery from spinal cord injury. Here, we investigated whether Wnt3a-secreting fibroblasts exert a favorable effect on spinal cord regeneration in spinal cord-injured rats. METHODS: Spinal cord injury (SCI) was induced in rats (n = 21) using an NYU impactor. One week after SCI, rats were assigned to a Wnt3a-secreting fibroblast transplantation group (Wnt group, n = 7), a L929 fibroblast transplantation group (vehicle group, n = 7), and contusion only group (sham group, n = 7). Motor function was tested weekly for 6 weeks. Manganese-enhanced magnetic resonance imaging (ME-MRI) was performed twice, once before cell transplantation and again 5 weeks after cell transplantation. After ME-MRI, expression of the axonal regeneration marker GAP-43 was assessed by immunohistochemistry (IHC). RESULTS: In the Wnt group, the mean Basso-Beattie-Bresnahan score was higher than that of the vehicle and sham groups throughout the observation period. The Wnt group also exhibited stronger signal intensity on ME-MRI, and IHC revealed that GAP-43 was highly expressed in the injured spinal cord in the Wnt group. CONCLUSIONS: These results strongly suggest that transplanted Wnt3a secreting fibroblasts promote axonal regeneration and functional improvement after SCI. Although further investigation will be necessary to clarify the intracellular mechanism by which Wnt signaling promotes axonal regeneration and functional improvement, this approach could be a highly promising therapeutic strategy for SCI.
