BIS-Biointerface Science in Regenerative Medicine, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Sci Rep. 2020 Nov 4;10(1):18988. doi: 10.1038/s41598-020-76019-z.
Learning rules by which cell shape impacts cell function would enable control of cell physiology and fate in medical applications, particularly, on the interface of cells and material of the implants. We defined the phenotypic response of human bone marrow-derived mesenchymal stem cells (hMSCs) to 2176 randomly generated surface topographies by probing basic functions such as migration, proliferation, protein synthesis, apoptosis, and differentiation using quantitative image analysis. Clustering the surfaces into 28 archetypical cell shapes, we found a very strict correlation between cell shape and physiological response and selected seven cell shapes to describe the molecular mechanism leading to phenotypic diversity. Transcriptomics analysis revealed a tight link between cell shape, molecular signatures, and phenotype. For instance, proliferation is strongly reduced in cells with limited spreading, resulting in down-regulation of genes involved in the G2/M cycle and subsequent quiescence, whereas cells with large filopodia are related to activation of early response genes and inhibition of the osteogenic process. In this paper we were aiming to identify a universal set of genes that regulate the material-induced phenotypical response of human mesenchymal stem cells. This will allow designing implants that can actively regulate cellular, molecular signalling through cell shape. Here we are proposing an approach to tackle this question.
通过学习细胞形状如何影响细胞功能的规则，我们可以在医学应用中控制细胞生理学和命运，特别是在细胞与植入材料的界面上。我们通过使用定量图像分析探测迁移、增殖、蛋白质合成、凋亡和分化等基本功能，定义了人类骨髓间充质干细胞（hMSCs）对 2176 种随机生成的表面形貌的表型反应。将表面聚类为 28 种典型细胞形状后，我们发现细胞形状与生理反应之间存在非常严格的相关性，并选择了七种细胞形状来描述导致表型多样性的分子机制。转录组学分析揭示了细胞形状、分子特征和表型之间的紧密联系。例如，在细胞扩散受限的情况下，增殖会大大降低，导致参与 G2/M 周期的基因下调，随后进入静止状态，而具有大量丝状伪足的细胞与早期反应基因的激活和成骨过程的抑制有关。在本文中，我们旨在确定一组通用基因，这些基因可以调节人类间充质干细胞对材料诱导的表型反应。这将允许设计可以通过细胞形状主动调节细胞、分子信号的植入物。在这里，我们提出了一种解决这个问题的方法。
