Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency.
Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency.
复制标题
DOI：
10.1016/j.biomaterials.2016.11.032
复制
发表时间：
2017-02
期刊：
影响因子：
14
通讯作者：
Dalby MJ
中科院分区：
文献类型：
--
作者：
Lee LC;Gadegaard N;de Andrés MC;Turner LA;Burgess KV;Yarwood SJ;Wells J;Salmeron-Sanchez M;Meek D;Oreffo RO;Dalby MJ
在培养中，分离的骨髓间充质干细胞（更准确地称为骨骼干细胞，SSC）自发分化为成纤维细胞，防止大量多能SSC生长用于再生医学。然而，调控精原干细胞扩增，同时保持多能性和防止成纤维细胞分化的机制知之甚少。理解SSC的维持是如何调节的主要障碍是（a）从骨髓分离的SSC是具有不同增殖特征的异质群体和（B）缺乏研究SSC数量扩增和多能性的工具。在这里，纳米形貌表面被用作允许SSC增殖同时保持多能性的工具。它表明，在文化中的SSC表型的保留需要调整的细胞周期，连接到有丝分裂原活化蛋白激酶的活化的变化。这表明生物材料可以提供跨SSC培养工具，并且确定SSC是否保留多能性或分化成成纤维细胞的生物过程在生化控制方面是微妙的，但在确定细胞命运方面是深刻的。
In culture isolated bone marrow mesenchymal stem cells (more precisely termed skeletal stem cells, SSCs) spontaneously differentiate into fibroblasts, preventing the growth of large numbers of multipotent SSCs for use in regenerative medicine. However, the mechanisms that regulate the expansion of SSCs, while maintaining multipotency and preventing fibroblastic differentiation are poorly understood. Major hurdles to understanding how the maintenance of SSCs is regulated are (a) SSCs isolated from bone marrow are heterogeneous populations with different proliferative characteristics and (b) a lack of tools to investigate SSC number expansion and multipotency. Here, a nanotopographical surface is used as a tool that permits SSC proliferation while maintaining multipotency. It is demonstrated that retention of SSC phenotype in culture requires adjustments to the cell cycle that are linked to changes in the activation of the mitogen activated protein kinases. This demonstrates that biomaterials can offer cross-SSC culture tools and that the biological processes that determine whether SSCs retain multipotency or differentiate into fibroblasts are subtle, in terms of biochemical control, but are profound in terms of determining cell fate.