Seizure suppression in amygdala-kindled mice by transplantation of neural stem/progenitor cells derived from mouse embryonic stem cells

Atsushi Shindo, Takehiro Nakamura, Yoshihito Matsumoto, Nobuyuki Kawai, Hideyuki Okano, Seigo Nagao, Toshifumi Itano, Takashi Tamiya

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Embryonic stem cells (ES cells) differentiate into multiple cell lineages including neural cells. The present study optimized the method to induce differentiation of gamma-aminobutyric acid-producing neurons (GABAergic neurons) from ES cell-derived neural stem/progenitor cells (NS/PCs), and transplanted these ES cell-derived GABAergic neurons producing neural progenitors into kindled epileptic mice, and analyzed the morphological and functional recovery from epilepsy. The response of kindling was evaluated by the modified Racine scale. Following stage 5 kindling, the mice were divided into two groups. Group 1 received NS/PCs derived from the ES cells ubiquitously expressing green fluorescent protein transplanted into the dorsal hippocampal area. Group 2 received microinjections of only the medium. After transplantation, the recovery of seizures was evaluated by the modified Racine scale again. All mice were perfused and fixed for immunohistochemical analysis after finishing the kindling experiment. In Group 1, one mouse was classified as stage 0, five as stage 3, and one as stage 4 recovering from stage 5 at 6 weeks after transplantation. In Group 2, all mice remained in stage 5. The transplanted cells were examined immunohistochemically using neuronal and GABAergic markers. In the transplanted mice, substantial hippocampal GABAergic re-innervation and seizure-suppressing effects were observed. NS/PCs derived from ES cells have high potential for use in transplantation therapy for clinically intractable epilepsies.

Original languageEnglish
Pages (from-to)98-105
Number of pages8
JournalNeurologia medico-chirurgica
Volume50
Issue number2
DOIs
Publication statusPublished - 2010 Feb

Keywords

  • Embryonic stem cell
  • Epilepsy
  • Gamma-aminobutyric acid
  • Kindling
  • Transplantation

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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