Abstract
The availability of signals to induce the appropriatedifferentiation of the transplanted and/or endogenous neural stem cells(NSCs) as well as the timing of the transplantation are important forsuccessful functional recovery of the damaged CNS. Due to the immediately post-traumatic microenvironment of the spinal cord, i.e. the transient upregulation of cytotoxic inflammatory cytokines including IL-6, the acute inflammatory stage is not favorable for the survival and neuronal differentiation of NSC transplants. Correspondingly, we could demonstrate that the optimal timing of NSC-transplantation is 1-2 weeks after injury, when the IL-6 expression is already downregulated. Furthermore, we could show that the neutralization of IL-6 signaling by the administration of blocking antibody in the acute phase of mouse model of spinal cord injury represents an attractive option for the treatment of spinal cord injury. In spite of these findings using rodents, a pre-clinical study using non-human primates is necessary before NSPCs can beused in clinical trials to treat human patients with spinal cord injury (SCI). Here, we show that human NSPCs grafted into spinal cords of adult common marmosets 9 days after contusion injury survived, differentiated into neurons, astrocytes, and oligodendrocytes, and eventually promotedfunctional recovery, suggesting that NSPC transplantation may be a feasible treatment for human SCI. [Jpn J Physiol 54 Suppl:S22 (2004)]
