組織工学と移植 Tissue Engineering and Transplantation

P2-1-110 経静脈的幹細胞投与による再生療法は，神経ネットワークの再構築により，アルコールによる脳障害を改善する Intravenous stem cell-based regenerative therapy cures brain impairment due to alcohol by reconstruction of neural network ○木川昌康1, 鵜飼渉1, 橋本恵理1, 白坂知彦1, 石井貴男1, 吉永敏弘1, 金田博雄1, 渡邊公彦1, 館農勝1, 齋藤利和1 ○Yoshiyasu Kigawa1, Wataru Ukai1, Eri Hashimoto1, Tomohiro Shirasaka1, Takao Ishii1, Toshihiro Yoshinaga1, Hiroo Kaneta1, Kimihiko Watanabe1, Masaru Tateno1, Toshikazu Saitou1 札幌医科大学医学部神経精神医学講座1 Dept Neuropsychiatry, Sapporo Med Univ, Sapporo1 Exposure of alcohol in fetal period does damage to the developing central nervous system (CNS) and can cause behavioral/cognitive and mental/social problems, defined as fetal alcohol spectrum disorders (FASDs). Abnormalities in cortical and limbic system development have been linked to FASD, but the underlying cellular pathogenesis in the brain remains elusive. A number of studies have found alterations in several presynaptic and postsynaptic components of the GABAergic systems, especially in reduced levels of GAD67 as observed in human and animal samples of FASD.Stem cell-based regenerative therapy promises great benefits for patients with incurable brain diseases. We studied the involvement of corticolimbic GABAergic interneuron disruption in cognitive and social impairment in FASD and the effect of stem cell treatment. We used an animal model of FASD created in fetal rats by the binge-like administration of ethanol during the peak of GABAergic cell generation of dams (E11-E14). We show that aspects of cognitive and social dysfunction are reversed by intravenous administration of fetal rat brain-derived neural stem cells (NSCs) at 45 days, a time point when neural developments are already completed. We also show that alterations of PV-containing GABAergic interneurons and synaptic density protein levels are essential for the therapeutic efficacy of intravenous NSC treatment in this animal model. Moreover we examine which the intravenous NSC treatment can improve CNS for a long period. We analyze the efficacy as morphological change of brain, the GABAergic systems and producing some neurotrophic factors.

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