Development of GPR40-positive neural stem cells for the brain restoration

开发用于大脑修复的 GPR40 阳性神经干细胞

• 批准号: 22390273
• 负责人: YAMASHIMA Tetsumori
• 金额: $ 12.15万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390273/
• 关键词: サル; 海馬; 骨髄幹細胞; GPR40; 多価不飽和脂肪酸; ドコサヘキサエン酸; ニューロン新生; 脳再生療法; ＣＡ-2，3; ＣＲＥＢ; ＢＤＮＦ; 苔状線維; シナプス; CREB; BDNF; TrkB; 骨髄間葉系幹細胞; bFGF; receptor internalization; サル; 海馬; 骨髄幹細胞; GPR40; 多価不飽和脂肪酸; ドコサヘキサエン酸; ニューロン新生; 脳再生療法; ＣＡ-2，3; ＣＲＥＢ; ＢＤＮＦ; 苔状線維; シナプス; CREB; BDNF; TrkB; 骨髄間葉系幹細胞; bFGF; receptor internalization

Vascular adventitia is a potential source of neuronal stem/progenitor cells in the neurogenic niche of adult monkey hippocampus, and the fatty acid receptor GPR40 is expressed here. As perivascular progenitors might be regarded as in situ counterparts of bone marrow stroma, we studied outcome of clonally-expanded bone marrow-derived multipotent mesenchymal stromal cells (BM-MSC) in response to DHA. During expansion the cell population was enriched in GPR40. DHA in addition to bFGF yielded a mature neuronal phenotype acquisition with a significant GPR40 up-regulation two weeks after culture. Compared to bFGF alone, there were not only quantitative but also temporally-relevant induction of neuronal specific transcripts and proteins. Along with the morphological changes and phenotype acquisition, DHA-dependent GPR40 up-regulation showed a cell cycle arrest implying ongoing differentiation. These data suggest that a DHA/GPR40-mediated mechanism may be involved in the adult neurogenesis.

血管外膜是成年猴海马的神经源性细胞中神经元干/祖细胞的潜在来源，此处表达了脂肪酸受体GPR40。由于血管周期祖细胞可能被认为是骨髓基质的原位对应物，因此我们研究了克隆膨胀的骨髓衍生的多蛋白间充质基质细胞（BM-MSC）的结果，响应于DHA。在扩张期间，细胞群在GPR40中富含。除了BFGF外，DHA还产生了成熟的神经元表型的获取，培养后两周内有明显的GPR40上调。与仅BFGF相比，不仅存在定量的，而且还具有与神经元特异性转录本和蛋白质相关的诱导。随着形态学的变化和表型的获取，DHA依赖性GPR40上调显示出细胞周期停滞意味着持续的分化。这些数据表明，DHA/GPR40介导的机制可能参与成人神经发生。