Collagen scaffold loaded allogeneic neural stem cells promoted locomotion recovery of spinal cord injury mainly through secreting neurotrophic factors

The combination of biological scaffold and neural stem cells (NSCs) is a promising treatment strategy for spinal cord injury (SCI). But adverse niche at injures spinal cord severe hamper the transplanted NSCs to preferentially differentiate neurons. In this study, we compared the therapeutic outcomes in rat completely transected SCI model after transplantations of collagen scaffold loaded with NSCs in different forms including unicellular NSCs, neurospheres, differentiated unicellular NSCs, and differentiated neurospheres. The results showed collagen scaffold combined each form of NSCs could markedly restore the motor function of the hindlimbs by Basso-Beattie-Bresnahan(BBB) scoring to similar levels. The transcriptome analysis showed there were similar expressions of neurotrophic factors among neurospheres, differentiated unicellular NSCs, and differentiated neurospere. Next, we enriched neurotrophic factors secreted from culture medium of these three forms of NSCs respectively and combined with collagen scaffold were transplanted into SCI to further assay therapeutic effects of secreting neurotrophic factors on SCI. BBB score analysis showed that the secreted neurotrophic factors from above three forms of NSCs had similar functional recovery of SCI. Therefore, we proposed that allogeneic NSCs transplant promotes functional recovery of SCI predominantly by secreting neurotrophic factors, not by direct neuronal replacement of differentiated neurons from transplanted cells.