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几何线索与RGD/BMP-2相互作用在引导干细胞命运中的作用

Interplay of Geometric Cues and RGD/BMP-2 Crosstalk in Directing Stem Cell Fate.

作者信息

Bilem Ibrahim, Chevallier Pascale, Plawinski Laurent, Sone Eli D, Durrieu Marie-Christine, Laroche Gaétan

机构信息

Laboratoire d'Ingénierie de Surface, Centre de Recherche sur les Matériaux Avancés, Département de Génie des Mines, de la Métallurgie et des Matériaux, Université Laval, 1065 Avenue de la médecine, Québec G1V 0A6, Canada.

Centre de Recherche du Centre Hospitalier Universitaire de Québec, Hôpital St-François d'Assise, 10 rue de l'Espinay, Québec G1L 3L5, Canada.

出版信息

ACS Biomater Sci Eng. 2017 Oct 9;3(10):2514-2523. doi: 10.1021/acsbiomaterials.7b00279. Epub 2017 Sep 5.

DOI:10.1021/acsbiomaterials.7b00279
PMID:33465907
Abstract

Within the native microenvironment, extracellular matrix (ECM) components are thought to display a complex and heterogeneous distribution, spanning several length scales. Herein, the objective is to mimic, in vitro, the hierarchical organization of proteins and growth factors as well as their crosstalk. Photolithography technique was used to adjacently pattern geometrically defined regions of RGD and BMP-2 mimetic peptides onto glass substrates. These ECM-derived ligands are known to jointly regulate mesenchymal stem cells (MSCs) osteogenic differentiation. By manipulating the spatial distribution of dually grafted peptides, the extent of human MSCs osteogenic differentiation was significantly affected, depending on the shape of peptide micropatterns. Our data highlight the existence of a strong interplay between geometric cues and biochemical signals. Such in vitro systems provide a valuable tool to investigate mechanisms by which multiple ECM cues overlap to regulate stem cell fate, thereby contributing to the design of bioinspired biomaterials for bone tissue engineering applications.

摘要

在天然微环境中,细胞外基质(ECM)成分被认为呈现出复杂且异质的分布,跨越多个长度尺度。在此,目标是在体外模拟蛋白质和生长因子的层次组织及其相互作用。使用光刻技术将RGD和BMP - 2模拟肽的几何定义区域相邻地图案化到玻璃基板上。已知这些源自ECM的配体共同调节间充质干细胞(MSC)的成骨分化。通过操纵双重接枝肽的空间分布,人MSC成骨分化的程度受到显著影响,这取决于肽微图案的形状。我们的数据突出了几何线索和生化信号之间存在强烈的相互作用。这种体外系统提供了一个有价值的工具,用于研究多种ECM线索重叠以调节干细胞命运的机制,从而有助于设计用于骨组织工程应用的仿生生物材料。

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