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Receptor-Targeted Magneto-Mechanical Stimulation of Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

机译:人骨髓源间充质干细胞成骨分化的受体靶向磁机械刺激。

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摘要

Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors—platelet-derived growth factor receptor α (PDGFRα) and integrin ανβ3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανβ3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation.
机译:在组织工程学和再生医学中,采用机械提示来促进干细胞分化和功能组织的形成。我们已经开发了一种磁力生物反应器(MFB),利用磁性微粒和纳米粒子靶向细胞表面受体,从而以皮牛顿水平向细胞传递高度靶向的局部力。在这项研究中,我们研究了磁性靶向和激活特定的两种机械敏感细胞膜受体-血小板衍生的生长因子受体α(PDGFRα)和整联蛋白ανβ3的作用。发现与最初的靶向整联蛋白ανβ3和未治疗的对照相比,在磁机械刺激与成骨培养基培养相结合三周后,通过最初靶向PDGFRα,可以获得更高的矿物质与基质的比率。此外,当在7天和12天的培养期内使用2天滞后的磁机械刺激时,不同的起始位点会引起差异的响应曲线。然而,与立即的磁机械刺激相比,两者均导致统计学上更高的成骨标记基因表达。这些结果为重要参数提供了见识,这些参数可用于设计适当的方案以通过磁机械致动进行离体诱导的骨形成。

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