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Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells

机译:三维球形空间边界条件差异性调控间充质基质细胞的成骨分化

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摘要

The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Mesenchymal stromal cells (MSCs) sensitively respond to alterations of mechanical cues generated from the SBC. However, mechanical cues provided by a three-dimensional (3D) environment are deprived in a reductionist 2D culture system. This study investigates how SBC affects osteogenic differentiation of MSCs using 3D scaffolds with monodispersed pores and homogenous spherical geometries. MSCs cultured under SBCs with diameters of 100 and 150 μm possessed the greatest capability of osteogenic differentiation. This phenomenon was strongly correlated with MSC morphology, organization of actin cytoskeleton, and distribution of focal adhesion involving α2 and α5 integrins. Further silencing either α2 or α5 integrin significantly reduced the above mentioned mechanosensitivity, indicating that the α2 and α5 integrins as mechano-sensitive molecules mediate MSCs’ ability to provide enhanced osteogenic differentiation in response to different spherical SBCs. Taken together, the findings provide new insights regarding how MSCs respond to mechanical cues from the surrounding microenvironment in a spherical SBC, and such biophysical stimuli should be taken into consideration in tissue engineering and regenerative medicine in conjunction with biochemical cues.
机译:由周围微环境引起的空间边界条件(SBC)施加了特定的几何形状和空间限制,影响器官发生和组织动态平衡。间充质基质细胞(MSC)敏感地响应从SBC产生的机械提示的变化。但是,在简化派2D文化系统中,缺乏由三维(3D)环境提供的机械提示。这项研究调查了SBC如何使用具有单分散孔和均一球形几何形状的3D支架影响MSC的成骨分化。在直径为100和150μm的SBCs下培养的MSC具有最大的成骨分化能力。这种现象与MSC形态,肌动蛋白细胞骨架的组织以及涉及α2和α5整联蛋白的粘着斑分布密切相关。进一步沉默α2或α5整联蛋白会显着降低上述机械敏感性,表明作为机械敏感分子的α2和α5整联蛋白介导MSC响应不同球形SBC提供增强的成骨分化能力。综上所述,这些发现提供了关于MSC如何响应球形SBC中来自周围微环境的机械提示的新见解,并且在组织工程和再生医学中应结合生物化学提示来考虑这种生物物理刺激。

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