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Recently, we have shown that the transplantation of spinal-cord-derived neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cords in adult rats, which may correspond to a behavioral recovery. To apply these results to clinical practice, a system for supplying human NSPCs on a large scale must be established. However, human spinal-cord-derived NSPCs are known to have a low proliferation rate, compared with forebrain-derived NSPCs. This low proliferative potency limits the feasibility of large-scale spinal cord-derived NSPC use. Thus, forebrain-derived NSPCs should be examined as an alternative to spinal-cord-derived NSPCs for the treatment of spinal cord injuries. In this study, we compared spinal-cord- and forebrain-derived NSPCs transplanted into injured spinal cords with respect to their fates in vivo as well as the animals' functional recovery. Both spinal-cord- and forebrain-derived NSPCs promoted functional recovery in rats with spinal cord injuries. While both spinal-cord- and forebrain-derived NSPCs survived, migrated and differentiated into neurons, astrocytes and oligodendrocytes in response to the microenvironment within the injured spinal cord after transplantation, forebrain-derived NSPCs differentiated into more neurons and fewer oligodendrocytes, compared to spinal-cord-derived NSPCs. Neurons that had differentiated from the transplanted forebrain-derived NSPCs were shown to be positive for neurotransmitters like GABA, glutamate and glycine, although authentic glycinergic neurons are not normally present within the forebrain. Thus, at least a subpopulation of the transplanted forebrain-derived NSPCs differentiated into spinal-cord-type neurons. In conclusion, forebrain-derived NSPCs could be used as an alternative to spinal-cord-derived NSPCs as a potential therapeutic agent for spinal cord injuries.

Comparison between Fetal Spinal-Cord- and Forebrain-Derived Neural Stem/Progenitor Cells as a Source of Transplantation for Spinal Cord Injury