School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
J Biosci Bioeng. 2010 Oct;110(4):479-86. doi: 10.1016/j.jbiosc.2010.05.009. Epub 2010 Jun 11.
Neural stem/progenitor cells (NSPCs) exhibit therapeutic potential in neuronal diseases. Previously, we reported that a sulfated polysaccharide (HS) from the sea cucumber Stichopus japonicus increased the proliferation of NSPCs. Since the formation of neurospheres is related with NSPCs proliferation, we investigated the mechanism leading to neurosphere formation with and without HS. The results showed that HS significantly promoted neurosphere formation in a dose-dependent manner at concentrations between 2 and 8 μg/ml. Cell cycle analysis showed that HS increased the percentage of cells in S phase by 2.8-fold, as compared with the control. On the other hand, we observed a significantly rapid aggregation of NSPCs, resulting in formation of neurospheres as early as 2 h after HS treatment. However, the aggregation was not caused by chemotactic migration of NSPCs, as evidenced by the transwell chamber assay. Furthermore, the effect of HS on NSPCs was similar to the tumor necrosis factor-α (TNF-α) that activated nuclear factor NF-κB. Thus, we demonstrated that HS was able to promote cell proliferation and aggregation of NSPCs which could lead to the formation of neurospheres, and suggested that HS can serve as an adjuvant for promoting proliferation of NSPCs and formation of neurospheres.
神经干细胞/祖细胞 (NSPCs) 在神经疾病中具有治疗潜力。之前，我们报道过，海参中的一种硫酸多糖 (HS) 可以增加 NSPCs 的增殖。由于神经球的形成与 NSPCs 的增殖有关，因此我们研究了 HS 存在和不存在时导致神经球形成的机制。结果表明，HS 以 2 至 8 μg/ml 的浓度剂量依赖性地显著促进神经球的形成。细胞周期分析表明，HS 使 S 期细胞的百分比增加了 2.8 倍，与对照组相比。另一方面，我们观察到 NSPCs 的聚集明显加快，导致 HS 处理后仅 2 小时即可形成神经球。然而，这种聚集不是由 NSPCs 的趋化性迁移引起的，这一点可以通过 Transwell 室测定得到证明。此外，HS 对 NSPCs 的作用类似于激活核因子 NF-κB 的肿瘤坏死因子-α (TNF-α)。因此，我们证明 HS 能够促进 NSPCs 的增殖和聚集，从而导致神经球的形成，并表明 HS 可以作为促进 NSPCs 增殖和神经球形成的佐剂。
