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微环境中神经元干/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视为骨髓基质的原位对应物，因此我们研究了克隆扩增的骨髓源性多能间充质基质细胞 (BM-MSC) 对 DHA 的反应结果。在扩增过程中，细胞群富含 GPR40。 DHA 和 bFGF 一起产生了成熟的神经元表型，培养两周后 GPR40 显着上调。与单独的 bFGF 相比，神经元特异性转录物和蛋白质不仅有定量的而且有时间相关的诱导。随着形态学变化和表型获得，DHA 依赖性 GPR40 上调显示细胞周期停滞，这意味着正在进行的分化。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.