Mechanical Environment Modulates Biological Properties of Oligodendrocyte Progenitor Cells
Mechanical Environment Modulates Biological Properties of Oligodendrocyte Progenitor Cells
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DOI：
10.1089/scd.2012.0189
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发表时间：
2012-11-01
影响因子：
4
通讯作者：
Franklin, Robin J. M.
中科院分区：
文献类型：
--
作者：
Jagielska, Anna;Norman, Adele L.;Franklin, Robin J. M.
髓鞘形成及其再生对应物髓鞘再生代表中枢神经系统（CNS）中最复杂的细胞-细胞相互作用之一。通过少突胶质细胞祖细胞（OPCs）的增殖、迁移和分化对轴突髓鞘形成的生物化学调节已被广泛表征。然而，大多数生物化学分析已经在体外进行的OPC粘附基质的刚度是数量级大于在体内CNS环境。在生理范围内机械性能的变化如何影响OPC生物学知之甚少。在这里，我们表明，OPC是机械敏感的。细胞在体外的存活、增殖、迁移和分化能力取决于聚合物水凝胶基质的机械刚度。这些性质中的大多数在CNS组织硬度的中间值处是最佳的。此外，在最佳刚度的凝胶上测量的细胞的许多这些特性与在玻璃或聚苯乙烯上测量的特性显著不同。OPC分化对细胞外环境的机械性能的依赖性提供了重新审视在非生理刚性表面上获得的结果的动机。我们还发现，OPCs在分化后会发生变化，但它们不会改变其顺应性以响应基质硬度，这与胚胎干细胞相似，但与成体干细胞不同。这些结果为进一步研究中枢神经系统细胞功能的机械生物学奠定了基础，并可能为慢性脱髓鞘疾病（如多发性硬化症）的髓鞘再生失败提供新的线索。
Myelination and its regenerative counterpart remyelination represent one of the most complex cell-cell interactions in the central nervous system (CNS). The biochemical regulation of axon myelination via the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPCs) has been characterized extensively. However, most biochemical analysis has been conducted in vitro on OPCs adhered to substrata of stiffness that is orders of magnitude greater than that of the in vivo CNS environment. Little is known of how variation in mechanical properties over the physiological range affects OPC biology. Here, we show that OPCs are mechanosensitive. Cell survival, proliferation, migration, and differentiation capacity in vitro depend on the mechanical stiffness of polymer hydrogel substrata. Most of these properties are optimal at the intermediate values of CNS tissue stiffness. Moreover, many of these properties measured for cells on gels of optimal stiffness differed significantly from those measured on glass or polystyrene. The dependence of OPC differentiation on the mechanical properties of the extracellular environment provides motivation to revisit results obtained on nonphysiological, rigid surfaces. We also find that OPCs stiffen upon differentiation, but that they do not change their compliance in response to substratum stiffness, which is similar to embryonic stem cells, but different from adult stem cells. These results form the basis for further investigations into the mechanobiology of cell function in the CNS and may specifically shed new light on the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis.