Microgrooved topographical surface directs tenogenic lineage specific differentiation of mouse tendon derived stem cells
Microgrooved topographical surface directs tenogenic lineage specific differentiation of mouse tendon derived stem cells
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微槽地形表面指导小鼠肌腱干细胞的肌腱谱系特异性分化
DOI：
10.1088/1748-605x/12/1/015013
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发表时间：
2017-02-01
影响因子：
4
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Shi, Yuan;Zhou, Kaili;Liu, Wei
肌腱源性干细胞（tendon derived stem cells，TDSCs）是肌腱细胞更新和肌腱功能维持的内源性细胞来源。它们也是肌腱工程和再生的重要细胞来源。此外，TDSC还通过其非腱源性谱系分化在肌腱病中发挥重要作用。研究表明，细胞形态决定间充质干细胞（MSC）的分化方向。在这项研究中，采用平行的微槽聚二甲基硅氧烷（PDMS）膜（10 µ m槽宽和3 µ m深）来研究通过这种特殊的地形表面在指导小鼠TDSC（mTDSC）谱系分化中的细胞伸长作用。结果显示，与在光滑PDMS膜上生长的铺展细胞相比，伸长的mTDSC表现出显著增强的肌腱形成标志物的基因表达，包括腱调节蛋白、巩膜轴、胶原蛋白I、III和VI、核心蛋白聚糖和腱生蛋白（p <0.05）。与此同时，与干细胞相关的基因Nanog、Sox 2和Oct4在伸长的mTDSC中的表达被显著抑制（p <0.05）。当在三系诱导分化下时，细胞伸长显著抑制mTDSC向成软骨谱系和成脂肪谱系的分化（p <0.05）。此外，细胞伸长可显著抑制BMP-2（一种肌腱病变模拟刺激剂）诱导的mTDSC成骨谱系分化（p <0.05）。总之，通过使用平行微槽形貌模拟天然肌腱结构可以促进mTDSC特异性向生腱谱系分化并防止非生腱谱系分化，从而为肌腱再生材料的设计提供了见解。
Tendon derived stem cells (TDSCs) are the endogenous cell source for tenocyte turnover and tendon functional maintenance. They are also the important cell source for tendon engineering and regeneration. In addition, TDSCs also play an important role in tendinopathy via their non-tenogenic lineage differentiation. It has been well demonstrated that cell shape could determine mesenchymal stem cell (MSC) lineage differentiation. In this study, a parallel microgrooved polydimethylsiloxane (PDMS) membrane (10 µm groove width and 3 µm depth) was employed to investigate the role of cell elongation via this particular topographic surface in directing murine TDSC (mTDSC) lineage differentiation. The results showed that elongated mTDSCs exhibited significantly enhanced the gene expression of tenogenic markers when compared to the spread cells that grew on smooth PDMS membrane including tenomodulin, scleraxis, collagens I, III, and VI, decorin and tenascin (p < 0.05). Meanwhile, stemness related genes such as Nanog, Sox2 and Oct4 were significantly inhibited for their expression in elongated mTDSCs (p < 0.05). When under tri-lineage induced differentiation, cell elongation significantly inhibited mTDSC differentiation towards chondrogenic and adipogenic lineages (p < 0.05). Furthermore, cell elongation could significantly inhibit mTDSC osteogenic lineage differentiation (p < 0.05) induced by BMP-2, a tendinopathy mimicking stimulant. In conclusion, simulation of native tendon structure via using parallel microgrooved topography can promote mTDSC differentiation specifically towards tenogenic lineage and prevent non-tenogenic lineage differentiation, providing an insight into the design of tendon regenerative materials.