Inhibition of Proliferation and Differentiation of Mesenchymal Stern Cells by Carboxylated Carbon Nanotubes
Inhibition of Proliferation and Differentiation of Mesenchymal Stern Cells by Carboxylated Carbon Nanotubes
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DOI：
10.1021/nn901479w
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发表时间：
2010-04-01
期刊：
影响因子：
17.1
通讯作者：
Yang, Mengsu
中科院分区：
文献类型：
--
作者：
Liu, Dandan;Yi, Changqing;Yang, Mengsu
多能间充质干细胞（Multipotent mesenchymal stem cells，MSCs）因其可连续传代和多向分化的特性，在干细胞治疗和组织工程领域受到广泛关注。碳纳米管（CNT）已被提议用作潜在的生物医学结构，用于骨形成。因此，研究MSCs与CNTs的相互作用机制具有重要意义。我们证明，羧化单壁碳纳米管（SWCNTs）和羧化多壁碳纳米管（MWCNTs）抑制骨髓间充质干细胞的增殖，成骨分化，成脂分化和矿化。氧化应激试验表明，活性氧（ROS）可能不是负责观察到的羧化碳纳米管的细胞毒性。定量实时聚合酶链反应（Q-PCR）实验证实，成骨细胞特异性基因和脂肪细胞分化特异性基因的表达大大减弱，在羧化碳纳米管的存在下，在骨髓间充质干细胞的分化。TEM图像显示，碳纳米管可能与位于细胞膜或细胞质中的蛋白质相互作用，这对随后的细胞信号通路产生进一步的影响。Q-PCR结果和Western blot分析一起验证了MSC的增殖和成骨分化的抑制可能通过Smad依赖的骨形态发生蛋白（BMP）信号通路来调节。
Multipotent mesenchymal stem cells (MSCs) have attracted substantial attention in stem cell therapy and tissue engineering due to their ability to be cultured for successive passages and multilineage differentiation. Carbon nanotubes (CNTs) have been proposed to be used as potential biomedical structures for bone formation. Therefore, it is important to study the mechanisms of interaction between MSCs and CNTs. We demonstrated that carboxylated single-walled carbon nanotubes (SWCNTs) and carboxylated multiwalled carbon nanotubes (MWCNTs) inhibited the proliferation, osteogenic differentiation, adipogenic differentiation, and mineralization of MSCs. Oxidative stress assay indicated that reactive oxygen species (ROS) may not be responsible for the observed cytotoxicity of carboxylated CNTs. Quantitative real-time polymerase chain reaction (Q-PCR) experiments confirmed that the expression of osteoblast specific genes and adipocyte differentiation specific genes was greatly attenuated during the differentiation of MSCs in the presence of carboxylated CNTs. TEM images revealed that CNTs might interact with proteins located on the cell membrane or in the cytoplasm, which have a further impact on subsequent cellular signaling pathways. Q-PCR results and Western blot analysis together verified that the inhibition of proliferation and osteogenic differentiation of MSCs may be modulated through a Smad-dependent bone morphogenetic protein (BMP) signaling pathway.