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

血管外膜是成年猴海马神经源性壁龛中神经干/祖细胞的潜在来源，脂肪酸受体GPR40在此表达。由于血管周围祖细胞可能被认为是骨髓基质的原位对应物，我们研究了克隆扩增的骨髓来源的多潜能间充质基质细胞(BM-MSC)对DHA的反应。在扩增过程中，GPR40丰富了细胞群体。除碱性成纤维细胞生长因子外，DHA还获得了成熟的神经元表型，培养两周后GPR40显著上调。与单独使用碱性成纤维细胞生长因子相比，不仅在数量上而且在时间上相关地诱导了神经元特异的转录物和蛋白。随着细胞形态的改变和表型的获得，依赖DHA的GPR40上调显示出细胞周期停滞，暗示着正在进行的分化。这些数据表明，DHA/GPR40介导的机制可能参与了成人神经发生。

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.