title: Seizure suppression in amygdala-kindled mice by transplantation of neural stem/progenitor cells derived from mouse embryonic stem cells.
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.
authors.affiliation: Department of Neurological Surgery, Kagawa University Faculty of Medicine, Kagawa.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shindo
authors.forename: Takehiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kawai
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Seigo
authors.initials: S
authors.lastname: Nagao
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Itano
authors.forename: Takashi
authors.initials: T
authors.lastname: Tamiya
mesh_terms: D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D007696:Kindling, Neurologic / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000503:physiopathology; D020127:Recovery of Function / Q000502:physiology; D013194:Staining and Labeling / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid