Kolind K, Kraft D, Bøggild T, Duch M, Lovmand J, Pedersen F S, Bindslev D A, Bünger C E, Foss M, Besenbacher F
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C, Denmark.
Department of Orthodontics, School of Dentistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Acta Biomater. 2014 Feb;10(2):641-50. doi: 10.1016/j.actbio.2013.11.006. Epub 2013 Nov 16.
The ability to control the behavior of stem cells provides crucial benefits, for example, in tissue engineering and toxicity/drug screening, which utilize the stem cell's capacity to engineer new tissues for regenerative purposes and the testing of new drugs in vitro. Recently, surface topography has been shown to influence stem cell differentiation; however, general trends are often difficult to establish due to differences in length scales, surface chemistries and detailed surface topographies. Here we apply a highly versatile screening approach to analyze the interplay of surface topographical parameters on cell attachment, morphology, proliferation and osteogenic differentiation of human mesenchymal dental-pulp-derived stem cells (DPSCs) cultured with and without osteogenic differentiation factors in the medium (ODM). Increasing the inter-pillar gap size from 1 to 6 μm for surfaces with small pillar sizes of 1 and 2 μm resulted in decreased proliferation and in more elongated cells with long pseudopodial protrusions. The same alterations of pillar topography, up to an inter-pillar gap size of 4 μm, also resulted in enhanced mineralization of DPSCs cultured without ODM, while no significant trend was observed for DPSCs cultured with ODM. Generally, cells cultured without ODM had a larger deposition of osteogenic markers on structured surfaces relative to the unstructured surfaces than what was found when culturing with ODM. We conclude that the topographical design of biomaterials can be optimized for the regulation of DPSC differentiation and speculate that the inclusion of ODM alters the ability of the cells to sense surface topographical cues. These results are essential in order to transfer the use of this highly proliferative, easily accessible stem cell into the clinic for use in cell therapy and regenerative medicine.
控制干细胞行为的能力具有至关重要的益处，例如在组织工程和毒性/药物筛选中，这些领域利用干细胞构建新组织以实现再生目的的能力以及在体外测试新药的能力。最近，已表明表面形貌会影响干细胞分化；然而，由于长度尺度、表面化学性质和详细表面形貌的差异，通常难以确定一般趋势。在这里，我们应用一种高度通用的筛选方法，来分析表面形貌参数对人牙髓间充质干细胞（DPSC）在有或无成骨分化因子（ODM）的培养基中培养时的细胞附着、形态、增殖和成骨分化的相互作用。对于柱尺寸为1和2μm的表面，将柱间间隙尺寸从1μm增加到6μm会导致增殖减少，细胞更细长且具有长伪足突起。柱形貌的相同变化，直至柱间间隙尺寸达到4μm，也导致在无ODM培养的DPSC矿化增强，而在有ODM培养的DPSC中未观察到明显趋势。一般来说，与有ODM培养相比，无ODM培养的细胞在结构化表面上的成骨标记物沉积相对于非结构化表面更大。我们得出结论，生物材料的形貌设计可针对DPSC分化的调控进行优化，并推测ODM的加入改变了细胞感知表面形貌线索的能力。这些结果对于将这种高度增殖、易于获取的干细胞用于细胞治疗和再生医学的临床应用至关重要。
