Dumont Courtney M, Piselli Jennifer M, Kazi Nadeem, Bowman Evan, Li Guoyun, Linhardt Robert J, Temple Sally, Dai Guohao, Thompson Deanna M
1 Department of Biomedical Engineering, Rensselaer Polytechnic Institute , Troy, New York.
2 Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York.
Stem Cells Dev. 2017 Aug 15;26(16):1199-1213. doi: 10.1089/scd.2016.0350. Epub 2017 Jul 20.
The microvasculature within the neural stem cell (NSC) niche promotes self-renewal and regulates lineage progression. Previous work identified endothelial-produced soluble factors as key regulators of neural progenitor cell (NPC) fate and proliferation; however, endothelial cells (ECs) are sensitive to local hemodynamics, and the effect of this key physiological process has not been defined. In this study, we evaluated adult mouse NPC response to soluble factors isolated from static or dynamic (flow) EC cultures. Endothelial factors generated under dynamic conditions significantly increased neuronal differentiation, while those released under static conditions stimulated oligodendrocyte differentiation. Flow increases EC release of neurogenic factors and of heparin sulfate glycosaminoglycans that increase their bioactivity, likely underlying the enhanced neuronal differentiation. Additionally, endothelial factors, especially from static conditions, promoted adherent growth. Together, our data suggest that blood flow may impact proliferation, adhesion, and the neuron-glial fate choice of adult NPCs, with implications for diseases and aging that reduce flow.
神经干细胞（NSC）生态位内的微血管系统促进自我更新并调节谱系进展。先前的研究确定内皮细胞产生的可溶性因子是神经祖细胞（NPC）命运和增殖的关键调节因子；然而，内皮细胞（ECs）对局部血流动力学敏感，而这一关键生理过程的影响尚未明确。在本研究中，我们评估了成年小鼠NPC对从静态或动态（流动）EC培养物中分离出的可溶性因子的反应。动态条件下产生的内皮因子显著增加神经元分化，而静态条件下释放的内皮因子则刺激少突胶质细胞分化。流动增加了神经源性因子和硫酸乙酰肝素糖胺聚糖的内皮细胞释放，从而增加了它们的生物活性，这可能是神经元分化增强的基础。此外，内皮因子，尤其是静态条件下产生的内皮因子，促进贴壁生长。总之，我们的数据表明血流可能影响成年NPC的增殖、黏附以及神经元-胶质细胞命运选择，这对减少血流的疾病和衰老具有重要意义。
