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Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency

机译:频繁的机械应力抑制来自人骨髓的间充质干细胞的增殖而不丧失多能性

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摘要

Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not onlyudto biochemical but also to physical cues, such as substrate topography and stiffness. To simulate theuddynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogateudsubstrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity canudbe adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown onudour hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrateudelasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergoudadipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover,udwe demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90%udwithout any loss of multiple lineage potential by changing the substrate elasticity every 2nd days.udSuch “dynamic in vitro niche” can be used not only for a better understanding of the role of dynamicudmechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stemudcells to a specific lineage.
机译:越来越多的证据表明,人间充质干细胞(hMSCs)不仅对生化有反应,而且还对物理提示(例如底物形貌和硬度)有反应。为了在体内模拟骨髓细胞外环境的动力学结构,我们基于物理交联的水凝胶设计了一种新型的骨髓衍生hMSC替代基质,其化学动力学可以动态地利用其弹性。在频繁的机械应力下,在水质凝胶底物上生长的hMSC在20 d内仍保持STRO-1的表达,而与底物的非弹性无关。暴露于相应的诱导培养基后,这些培养的​​hMSC可以进行成胶和成骨,而无需将细胞转移到其他底物上。此外, udwe证明了我们的替代底物可通过每隔2天改变底物弹性来抑制hMSCs的增殖达90% ud,而不会丧失多谱系潜能。 ud这种“动态体外生态位”不仅可以用于更好地了解了动态力学应力对hMSC命运的作用,而且还了解了成体干 udcells向特定谱系的同步分化。

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