Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Acta Biomater. 2013 Apr;9(4):6041-51. doi: 10.1016/j.actbio.2012.12.007. Epub 2012 Dec 11.
Mesenchymal stem cells (MSCs) can generate chondrocytes in vitro, but typically need to be cultured as aggregates in the presence of transforming growth factor beta (TGF-β), which makes scale-up difficult. Here we investigated if polyacrylate substrates modelled on the functional group composition and distribution of the Arg-Gly-Asp (RGD) integrin-binding site could induce MSCs to undergo chondrogenesis in the absence of exogenous TGF-β. Within a few days of culture on the biomimetic polyacrylates, both mouse and human MSCs, and a mesenchymal-like mouse-kidney-derived stem cell line, began to form multi-layered aggregates and started to express the chondrocyte-specific markers, Sox9, collagen II and aggrecan. Moreover, collagen II tended to be expressed in the centre of the aggregates, similarly to developing limb buds in vivo. Surface analysis of the substrates indicated that those with the highest surface amine content were most effective at promoting MSC chondrogenesis. These results highlight the importance of surface group functionality and the distribution of those groups in the design of substrates to induce MSC chondrogenesis.
间充质干细胞(MSCs)可以在体外生成软骨细胞,但通常需要在转化生长因子β(TGF-β)存在下培养成聚集物,这使得规模扩大变得困难。在这里,我们研究了基于 Arg-Gly-Asp(RGD)整合素结合位点的功能基团组成和分布的聚丙烯酸酯底物是否可以在没有外源性 TGF-β的情况下诱导 MSCs 发生软骨生成。在生物模拟聚丙烯酸酯上培养几天内,无论是小鼠还是人 MSCs,以及一种类似于间充质的小鼠肾脏来源的干细胞系,开始形成多层聚集物,并开始表达软骨细胞特异性标志物 Sox9、胶原 II 和聚集蛋白聚糖。此外,胶原 II 倾向于在聚集物的中心表达,类似于体内发育中的肢体芽。对底物的表面分析表明,表面胺含量最高的底物最有效地促进 MSC 软骨生成。这些结果强调了表面基团功能和这些基团在诱导 MSC 软骨生成的底物设计中的分布的重要性。