Silica-Coated Magnetic Nanoparticles Decrease Human Bone Marrow-Derived Mesenchymal Stem Cell Migratory Activity by Reducing Membrane Fluidity and Impairing Focal Adhesion
Silica-Coated Magnetic Nanoparticles Decrease Human Bone Marrow-Derived Mesenchymal Stem Cell Migratory Activity by Reducing Membrane Fluidity and Impairing Focal Adhesion
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DOI：
10.3390/nano9101475
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发表时间：
2019-10-01
期刊：
影响因子：
5.3
通讯作者：
Lee, Gwang
中科院分区：
文献类型：
--
作者：
Shin, Tae Hwan;Lee, Da Yeon;Lee, Gwang
对于基于干细胞的治疗，应使用非侵入性或组织学方法和基于纳米材料的标记剂追踪干细胞的命运和分布。然而，评估纳米材料在干细胞中的生物物理效应和相关生物功能仍然具有挑战性。在这里，我们的目的是研究纳米材料对干细胞的生物物理效应，包括膜流动性，使用全内反射荧光显微镜，和牵引力，使用微柱的人骨髓间充质干细胞（hBM-MSCs）标记与二氧化硅涂层的磁性纳米粒子纳入罗丹明B异硫氰酸酯（MNPs@SiO2（RITC））。此外，为了评估与这些生物物理变化相关的生物学功能，我们评估了MNPs@SiO2（RITC）处理的hBM-MSCs的细胞活力、活性氧（ROS）产生、细胞内细胞骨架和迁移活性。与对照组相比，细胞活力降低了10%，细胞内ROS增加了2倍，这是由于在用1.0 μ g/μ L MNPs@SiO2（RITC）处理的hBM-MSC中诱导了20%的高过氧化脂质。MNPs@SiO2（RITC）诱导的脂质氧化以浓度依赖性方式降低膜流动性。此外，在用1.0 μ g/μ L MNPs@SiO2（RITC）处理的细胞中观察到细胞收缩，伴有局灶性粘连的异常形成，总牵引力降低约30%，而MNPs@SiO2（RITC）与细胞骨架蛋白之间没有特异性相互作用。此外，与细胞膜流动性和细胞骨架异常高度相关的hBM-MSCs的迁移活性在MNPs@SiO2（RITC）处理后显著降低。这些观察结果表明，由于干细胞生物物理特性和相关生物学功能的变化，MNPs@SiO2（RITC）处理损害了hBM-MSC的迁移活性，突出了纳米颗粒损害hBM-MSC迁移的重要机制。我们的研究结果表明，用于干细胞运输或临床应用的纳米颗粒应使用最佳纳米颗粒浓度进行标记，以保持hBM-MSC迁移活性，并确保干细胞定位后的成功结果。
For stem cell-based therapies, the fate and distribution of stem cells should be traced using non-invasive or histological methods and a nanomaterial-based labelling agent. However, evaluation of the biophysical effects and related biological functions of nanomaterials in stem cells remains challenging. Here, we aimed to investigate the biophysical effects of nanomaterials on stem cells, including those on membrane fluidity, using total internal reflection fluorescence microscopy, and traction force, using micropillars of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) labelled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate (MNPs@SiO2(RITC)). Furthermore, to evaluate the biological functions related to these biophysical changes, we assessed the cell viability, reactive oxygen species (ROS) generation, intracellular cytoskeleton, and the migratory activity of MNPs@SiO2(RITC)-treated hBM-MSCs. Compared to that in the control, cell viability decreased by 10% and intracellular ROS increased by 2-fold due to the induction of 20% higher peroxidized lipid in hBM-MSCs treated with 1.0 mu g/mu L MNPs@SiO2(RITC). Membrane fluidity was reduced by MNPs@SiO2(RITC)-induced lipid oxidation in a concentration-dependent manner. In addition, cell shrinkage with abnormal formation of focal adhesions and similar to 30% decreased total traction force were observed in cells treated with 1.0 mu g/mu L MNPs@SiO2(RITC) without specific interaction between MNPs@SiO2(RITC) and cytoskeletal proteins. Furthermore, the migratory activity of hBM-MSCs, which was highly related to membrane fluidity and cytoskeletal abnormality, decreased significantly after MNPs@SiO2(RITC) treatment. These observations indicated that the migratory activity of hBM-MSCs was impaired by MNPs@SiO2(RITC) treatment due to changes in stem-cell biophysical properties and related biological functions, highlighting the important mechanisms via which nanoparticles impair migration of hBM-MSCs. Our findings indicate that nanoparticles used for stem cell trafficking or clinical applications should be labelled using optimal nanoparticle concentrations to preserve hBM-MSC migratory activity and ensure successful outcomes following stem cell localisation.