Pathology

Biography

Biography: Masahiko Abematsu

Abstract

Neural stem cells (NSCs) possess the ability to self-renew and to differentiate into the three major cell types found in the central nervous system (CNS). Recent studies have shown that epigenetic gene regulation events such as DNA methylation and histone modification play important roles in regulating NSC fate specification. In this presentation, we have previously shown that the histone deacetylase inhibitor valproic acid (VPA) enhances neuronal differentiation of NSCs. Perhaps because these patterns of NSC differentiation are exquisitely controlled during normal embryonic development, restoration of damaged neural networks in the injured adult CNS is severely limited. Here, using a mouse model of spinal cord injury (SCI), we show that transplanting NSCs and administering VPA enhances the functional recovery of their hindlimbs. Neuronal differentiation of transplanted NSCs was promoted in VPA-treated mice. Anterograde corticospinal tract tracing revealed that transplant-derived neurons partially reconstructed the broken neuronal circuits, most likely in a ‘relay’ manner. Ablation of the transplanted cells abolished the recovery of hindlimb motor function, indicating that transplanted cells contributed directly to the improvement of motor function. These data raise the possibility that epigenetic regulation in transplanted neural stem cells can be exploited to provide treatment for SCI.