Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury

Masahiko Abematsu, Keita Tsujimura, Mariko Yamano, Michiko Saito, Kenji Kohno, Jun Kohyama, Masakazu Namihira, Setsuro Komiya, Kinichi Nakashima

研究成果: Contribution to journalArticle査読

192 被引用数 (Scopus)

抄録

The body's capacity to restore damaged neural networks in the injured CNS is severely limited. Although various treatment regimens can partially alleviate spinal cord injury (SCI), the mechanisms responsible for symptomatic improvement remain elusive. Here, using a mouse model of SCI, we have shown that transplantation of neural stem cells (NSCs) together with administration of valproic acid (VPA), a known antiepileptic and histone deacetylase inhibitor, dramatically enhanced the restoration of hind limb function. VPA treatment promoted the differentiation of transplanted NSCs into neurons rather than glial cells. Transsynaptic anterograde corticospinal tract tracing revealed that transplant-derived neurons reconstructed broken neuronal circuits, and electron microscopic analysis revealed that the transplant-derived neurons both received and sent synaptic connections to endogenous neurons. Ablation of the transplanted cells abolished the recovery of hind limb motor function, confirming that NSC transplantation directly contributed to restored motor function. These findings raise the possibility that epigenetic status in transplanted NSCs can be manipulated to provide effective treatment for SCI.

本文言語英語
ページ(範囲)3255-3266
ページ数12
ジャーナルJournal of Clinical Investigation
120
9
DOI
出版ステータス出版済み - 9 1 2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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