Seizure Suppression in Amygdala-Kindled Mice by Transplantation of Neural Stem/Progenitor Cells Derived From Mouse Embryonic Stem Cells

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概要

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• 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.

• 2010-02-15

著者

• SHINDO Atsushi

  Department of Neurological Surgery, Kagawa University Faculty of Medicine

• NAKAMURA Takehiro

  Department of Neurobiology, Kagawa University Faculty of Medicine

• MATSUMOTO Yoshihito

  Department of Neurological Surgery, Kagawa University Faculty of Medicine

• KAWAI Nobuyuki

  Department of Neurological Surgery, Kagawa University Faculty of Medicine

• OKANO Hideyuki

  Department of Physiology, Keio University School of Medicine

• NAGAO Seigo

  Department of Neurological Surgery, Kagawa University Faculty of Medicine

• ITANO Toshifumi

  Department of Neurobiology, Kagawa University Faculty of Medicine

• TAMIYA Takashi

  Department of Neurological Surgery, Kagawa University Faculty of Medicine

• 中村 丈洋

  香川大学医学部脳神経生物学

• Nagao Seigo

  香川大学 医学部脳神経外科

• Nagao Seigo

  Department Of Neurological Surgery Kagawa University Faculty Of Medicine

• Nagao S

  Department Of Neurological Surgery Kagawa University School Of Medicine

• Nagao S

  Department Of Neurological Surgery Kagawa University

• Nagao Seigo

  Department Of Neurological Surgery Kagawa Medical School

• Kawai Nobuyuki

  香川大学 医学部脳神経外科

• Kawai Nobuyuki

  Department Of Neurological Surgery Kagawa University Faculty Of Medicine

• Tamiya Takashi

  香川大学 医学部脳神経外科

• Tamiya Takashi

  Department Of Neurological Surgery Kagawa University Faculty Of Medicine

• Nakamura Takehiro

  Department Of Neurobiology Kagawa University Faculty Of Medicine

• Shindo Atsushi

  Department Of Neurological Surgery Kagawa University Faculty Of Medicine

• Nagao Seigo

  Department Of Neurological Surgery Kagawa University School Of Medicine

• Tamiya Takashi

  Department Of Neurological Surgery Kagawa University School Of Medicine

• Nakamura Takehiro

  Department Of Applied Chemistry Faculty Of Science And Technology Keio University

• Itano Toshifumi

  Department Of Neurobiology Kagawa University Faculty Of Medicine

• Itano Toshifumi

  Department Of Biology Kagawa Medical School

• Kawai Nobuyuki

  Department Of Neurological Surgery Kagawa University School Of Medicine

• Okano Hideyuki

  Department Of Neuroanatomy Biomedical Research Center Osaka University Medical School

• Tamiya Takashi

  Department Of Neurological Surgery Faculty Of Medicine Kagawa University

• Matsumoto Yoshihito

  Department Of Neurological Surgery Kagawa University Faculty Of Medicine

• Kawai Nobuyuki

  Department Of Neurological Surgery Kagawa Medical School

• Kawai Nobuyuki

  Department Of Medical Physics Faculty Of Medicine Kagawa University

• Okano Hideyuki

  Department Of Molecular Neurobiology Institute Of Basic Medical Sciences And Center For Tara(tsukuba

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