Atypical Mesenchymal Stromal Cell Responses to Topographic Modifications of Titanium Biomaterials Indicate Cytoskeletal- and Genetic Plasticity-Based Heterogeneity of Cells
Atypical Mesenchymal Stromal Cell Responses to Topographic Modifications of Titanium Biomaterials Indicate Cytoskeletal- and Genetic Plasticity-Based Heterogeneity of Cells
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DOI：
10.1155/2019/5214501
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发表时间：
2019-07-01
影响因子：
4.3
通讯作者：
Brett, Peter M.
中科院分区：
文献类型：
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作者：
Khan, Mohammad R.;Mordan, Nicola;Brett, Peter M.
钛（Ti）由于其相对惰性的表面氧化层，使植入装置能够组装组织修复成分，最终实现骨整合，因此被广泛用作骨内植入物的生物材料。微纳米结构形式的地形改变显著促进成体间充质基质细胞（MSCs）的骨整合和成骨分化。虽然组织和细胞对钛表面修饰的差异反应的核心生物学机制尚不清楚，但粘附和形态适应是细胞-生物材料界面最早发生的事件之一，受到表面形貌的高度影响，并深刻影响干细胞命运决定的调节。本研究将钛的形貌改变对人间充质干细胞粘附和形态适应的影响与表型变化联系起来。结果表明，经过修饰的钛拓扑结构阻止了一部分间充质干细胞的粘附，同时对粘附细胞产生了明显的形态学限制。这些影响异常地与干细胞多能性和Wnt信号相关标记在两种修饰表面上的差异表达相对应，同时在疏水性和亲水性表面修饰之间存在差异——尽管与抛光钛相比，两种修饰的地形诱导的成骨分化程度产生了同样显著的更高水平的细胞矿化。这些结果表明，在缺乏沉积蛋白和可溶性因子的情况下，这两种修饰的地形都会导致具有相对较高细胞骨架可塑性的祖细胞亚群的选择性粘附。虽然沉积蛋白和可溶性因子的存在不会显著影响细胞的粘附性，但纳米形貌修饰增强了增殖条件下多能性标志物的表达，相反，在成骨诱导条件下，这两种修饰的形貌会覆盖多能性标志物。进一步破译细胞选择性和钛地形响应的机制将提高我们对干细胞异质性的理解，并推进MSCs在再生医学中的潜力。
Titanium (Ti) is widely used as a biomaterial for endosseous implants due to its relatively inert surface oxide layer that enables implanted devices the ability of assembling tissue reparative components that culminate in osseointegration. Topographic modifications in the form of micro- and nanoscaled structures significantly promote osseointegration and enhance the osteogenic differentiation of adult mesenchymal stromal cells (MSCs). While the biological mechanisms central to the differential responses of tissues and cells to Ti surface modifications remain unknown, adhesion and morphological adaptation are amongst the earliest events at the cell-biomaterial interface that are highly influenced by surface topography and profoundly impact the regulation of stem cell fate determination. This study correlated the effects of Ti topographic modifications on adhesion and morphological adaptation of human MSCs with phenotypic change. The results showed that modified Ti topographies precluded the adhesion of a subset of MSCs while incurring distinct morphological constraints on adherent cells. These effects anomalously corresponded with a differential expression of stem cell pluripotency and Wnt signalling-associated markers on both modified surfaces while additionally differing between hydrophobic and hydrophilic surface modifications-though extent of osteogenic differentiation induced by both modified topographies yielded similarly significant higher levels of cellular mineralisation in contrast to polished Ti. These results suggest that in the absence of deposited proteins and soluble factors, both modified topographies incur the selective adhesion of a subpopulation of progenitors with relatively higher cytoskeletal plasticity. While the presence of deposited proteins and soluble factors does not significantly affect adherence of cells, nanotopographic modifications enhance expression of pluripotency markers in proliferative conditions, which are conversely overridden by both modified topographies in osteogenic inductive conditions. Further deciphering the mechanisms underlying cellular selectivity and Ti topographic responsiveness will improve our understanding of stem cell heterogeneity and advance the potential of MSCs in regenerative medicine.