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Cell-matrix interactions regulate mesenchymal stem cell response to hydrostatic pressure

机译:细胞-基质相互作用调节间充质干细胞对静水压力的反应

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Both hydrostatic pressure (HP) and cell-matrix interactions have independently been shown to regulate the chondrogenic differentiation of mesenchymal stem cells (MSCs). The objective of this study was to test the hypothesis that the response of MSCs to hydrostatic pressure will depend on the biomaterial within which the cells are encapsulated. Bone-marrow-derived MSCs were seeded into either agarose or fibrin hydrogels and exposed to 10 MPa of cyclic HP (1 Hz, 4 h per day, 5 days per week for 3 weeks) in the presence of either 1 or 10 ng ml -1 of TGF-β3. Agarose hydrogels were found to support a spherical cellular morphology, while MSCs seeded into fibrin hydrogels attached and spread, with clear stress fiber formation. Hydrogel contraction was also observed in MSC-fibrin constructs. While agarose hydrogels better supported chondrogenesis of MSCs, HP only enhanced sulfated glycosaminoglycan (sGAG) accumulation in fibrin hydrogels, which correlated with a reduction in fibrin contraction. HP also reduced alkaline phosphatase activity in the media for both agarose and fibrin constructs, suggesting that this stimulus plays a role in the maintenance of the chondrogenic phenotype. This study demonstrates that a complex relationship exists between cell-matrix interactions and hydrostatic pressure, which plays a key role in regulating the chondrogenic differentiation of MSCs.
机译:静水压(HP)和细胞-基质相互作用都已独立显示调节间充质干细胞(MSCs)的软骨分化。这项研究的目的是检验以下假设,即MSC对静水压力的响应将取决于包裹细胞的生物材料。将骨髓来源的MSCs接种到琼脂糖或纤维蛋白水凝胶中,并在存在1或10 ng ml-的条件下,暴露于10 MPa的环状HP中(1 Hz,每天4 h,每周5天,持续3周)- TGF-β3中的1个。发现琼脂糖水凝胶可支持球形细胞形态,而将MSCs植入附着并扩散的血纤蛋白水凝胶中,形成清晰的应力纤维。在MSC-纤维蛋白构建物中也观察到水凝胶收缩。虽然琼脂糖水凝胶更好地支持了MSC的软骨形成,但HP仅增强了纤维蛋白水凝胶中的硫酸化糖胺聚糖(sGAG)积累,这与纤维蛋白收缩的减少有关。 HP还降低了琼脂糖和血纤蛋白构建体在培养基中的碱性磷酸酶活性,这表明该刺激在维持软骨形成表型中起作用。这项研究表明,细胞-基质相互作用与静水压力之间存在复杂的关系,这在调节MSC的软骨形成分化中起着关键作用。

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