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磁场纳米粒子对细胞施加的张力调节人骨髓间充质干细胞的分化。

Tension exerted on cells by magnetic nanoparticles regulates differentiation of human mesenchymal stem cells.

机构信息

School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

School of Biological Sciences and Institute for Molecular Biology and Genetics, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

出版信息

Biomater Adv. 2022 Aug;139:213028. doi: 10.1016/j.bioadv.2022.213028. Epub 2022 Jul 19.

Abstract

Cells can 'sense' physical cues in the surrounding microenvironment and 'react' by changing their function. Previous studies have focused on regulating the physical properties of the matrix, such as stiffness and topography, thus changing the tension 'felt' by the cell as a result. In this study, by directly applying a quantified magnetic force to the cell, a correlation between differentiation and tension was shown. The magnetic force, quantified by magnetic tweezers, was applied by incorporating magnetotactic bacteria-isolated magnetic nanoparticles (MNPs) in human mesenchymal stem cells. As the applied tension increased, the expression levels of osteogenic differentiation marker genes and proteins were proportionally upregulated. Additionally, the translocation of YAP and RUNX2, deformation of nucleus, and activation of the MAPK signaling pathway were observed in tension-based osteogenic differentiation. Our findings provide a platform for the quantitative control of tension, a key factor in stem cell differentiation, between cells and the matrix using MNPs. Furthermore, these findings improve the understanding of osteogenic differentiation by mechanotransduction.

摘要

细胞可以“感知”周围微环境中的物理线索,并通过改变其功能“做出反应”。以前的研究主要集中在调节基质的物理性质,如刚度和形貌,从而改变细胞感受到的张力。在这项研究中,通过直接向细胞施加量化的磁力,显示了分化与张力之间的相关性。通过将分离出的磁细菌的磁性纳米颗粒 (MNPs) 整合到人骨髓间充质干细胞中,利用磁镊量化了磁力。随着施加的张力增加,成骨分化标记基因和蛋白质的表达水平呈比例上调。此外,在基于张力的成骨分化中观察到 YAP 和 RUNX2 的易位、核的变形以及 MAPK 信号通路的激活。我们的研究结果为使用 MNPs 在细胞和基质之间进行干细胞分化的关键因素——张力的定量控制提供了一个平台。此外,这些发现通过机械转导提高了对成骨分化的理解。

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