Neural stem cells (NSCs) transplantation is regarded as a promising therapeutic strategy to treat severe spinal cord injury (SCI) by compensating the neuronal loss. However, significant challenges including long-term survival, directed neuronal differentiation, and functional integration of the transplanted NSCs and their progenies within the host spinal cord are yet to be solved. In this study, NSCs are trained on differently modified collagen scaffolds to increase their neuronal differentiation rate when cultured under the simulated SCI microenvironment. Then, a functional scaffold is screened out, on which the cultured NSCs show high neuronal differentiation rate and generate both sensory and motor mature neurons. Subsequently, that NSC seeded functional scaffold is transplanted into a rat severe SCI model. The results show that higher endogenous neurogenesis efficiency as well as in vivo survival and neuronal differentiation rate of the grafted NSCs are observed. Moreover, both sensory and motor neurons are found to be differentiated from the grafted NSCs in the lesion site and those newly generated neurons can functionally interact with each other and the host neurons. Taken together, the in vitro training systems for modulating the differentiation profiles of NSCs are instructive and exhibit strong potentials for SCI treatments.

 

Keywords:collagen scaffold;functional recovery;neural stem cells;neuronal differentiation;spinal cord injury