Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency.
Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency.
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DOI：
10.1038/srep24264
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发表时间：
2016-04-15
影响因子：
4.6
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Frank V;Kaufmann S;Wright R;Horn P;Yoshikawa HY;Wuchter P;Madsen J;Lewis AL;Armes SP;Ho AD;Tanaka M
越来越多的证据表明，人类间充质干细胞（hMSCs）不仅对生物化学，而且对物理线索，如基质地形和刚度。为了模拟体内骨髓细胞外环境的动态结构，我们设计了一种基于物理交联水凝胶的新型骨髓源性hMSCs替代基质，其弹性可以通过化学刺激动态地采用。在频繁的机械应力下，在我们的水凝胶基质上生长的hMSCs在20 d内保持STRO-1的表达，而不管基质的弹性如何。在暴露于相应的诱导培养基时，这些培养的hMSC可以经历脂肪生成和成骨，而不需要将细胞转移到其他基质上。此外，我们证明了我们的替代底物通过每2天改变底物弹性抑制hMSC的增殖高达90%，而没有任何多谱系潜力的损失。这种“动态体外生态位”不仅可以用于更好地理解动态机械应力对hMSCs命运的作用，而且可以用于成体干细胞向特定谱系的同步分化。
Mounting evidence indicated that human mesenchymal stem cells (hMSCs) are responsive not only to biochemical but also to physical cues, such as substrate topography and stiffness. To simulate the dynamic structures of extracellular environments of the marrow in vivo, we designed a novel surrogate substrate for marrow derived hMSCs based on physically cross-linked hydrogels whose elasticity can be adopted dynamically by chemical stimuli. Under frequent mechanical stress, hMSCs grown on our hydrogel substrates maintain the expression of STRO-1 over 20 d, irrespective of the substrate elasticity. On exposure to the corresponding induction media, these cultured hMSCs can undergo adipogenesis and osteogenesis without requiring cell transfer onto other substrates. Moreover, we demonstrated that our surrogate substrate suppresses the proliferation of hMSCs by up to 90% without any loss of multiple lineage potential by changing the substrate elasticity every 2nd days. Such “dynamic in vitro niche” can be used not only for a better understanding of the role of dynamic mechanical stresses on the fate of hMSCs but also for the synchronized differentiation of adult stem cells to a specific lineage.