The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells
The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells
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DOI：
10.1016/j.taap.2010.03.011
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发表时间：
2010-06-01
影响因子：
3.8
通讯作者：
Huang, Dong-Ming
中科院分区：
文献类型：
--
作者：
Chen, Ying-Chun;Hsiao, Jong-Kai;Huang, Dong-Ming
超顺磁性氧化铁（SPIO）纳米颗粒对于监测体内细胞运输和区分细胞再生是否起源于外源性细胞来源非常有用，这是开发成功的干细胞疗法的关键问题。然而，SPIO标记对干细胞行为的影响仍然不确定。在这里，我们展示了Ferucarbotran（一种离子SPIO）对人间充质干细胞成骨分化及其信号传导机制的抑制作用。Ferucarbotran引起成骨分化的剂量依赖性抑制，在高浓度下消除分化，促进细胞迁移，并激活信号分子β-连环蛋白、癌/睾丸抗原、SSX和基质金属蛋白酶2（MMP 2）。铁螯合剂去铁胺抑制了所有上述Ferucarbotran诱导的作用，证明了游离铁在抑制成骨分化中的重要作用，所述成骨分化由促进细胞动员介导，涉及特定信号传导途径的激活。(C)2010年爱思唯尔公司All rights reserved.
Superparamagnetic iron oxide (SPIO) nanoparticles are very useful for monitoring cell trafficking in vivo and distinguish whether cellular regeneration originated from an exogenous cell source, which is a key issue for developing successful stem cell therapies. However, the impact of SPIO labeling on stem cell behavior remains uncertain. Here, we show the inhibitory effect of Ferucarbotran, an ionic SPIO, on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. Ferucarbotran caused a dose-dependent inhibition of osteogenic differentiation, abolished the differentiation at high concentration, promoted cell migration, and activated the signaling molecules, beta-catenin, a cancer/testis antigen, SSX, and matrix metalloproteinase 2 (MMP2). An iron chelator, desferrioxamine, suppressed all the above Ferucarbotran-induced actions, demonstrating an important role of free iron in the inhibition of osteogenic differentiation that is mediated by the promotion of cell mobilization, involving the activation of a specific signaling pathway. (C) 2010 Elsevier Inc. All rights reserved.