Tenogenic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells dictated by properties of braided submicron fibrous scaffolds
Tenogenic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells dictated by properties of braided submicron fibrous scaffolds
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DOI：
10.1016/j.biomaterials.2014.05.006
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发表时间：
2014-08-01
期刊：
影响因子：
14
通讯作者：
Li, Wan-Ju
中科院分区：
文献类型：
--
作者：
Czaplewski, Sarah K.;Tsai, Tsung-Lin;Li, Wan-Ju
肌腱和韧带（T/L）工程是一个不断发展的研究领域，有潜力解决当前肌腱和韧带缺陷治疗的不足之处。我们的团队先前开发了编织亚微米纤维支架（BSMFSs），并证明了BSMFSs在肌腱和韧带组织工程中的可行性。本研究的目的是探究纤维化学成分和编织角度对BSMFS力学性能的影响，进而探究在无肌腱诱导培养基的情况下，接种在BSMFS上的人诱导多能干细胞衍生的间充质干细胞（hiPSC - MSCs）在循环拉伸刺激下向肌腱分化的情况。通过改变纤维化学成分和/或编织角度，制备出了具有一系列力学性能的BSMFSs。我们发现纤维化学成分决定细胞黏附，而编织角度决定hiPSC - MSCs的组织特异性谱系分化。与小角度编织的支架相比，大角度编织的支架能更好地支持hiPSC - MSC向肌腱分化，这体现在肌腱/韧带相关标志物的产生、成骨标志物的下调以及呈现成纤维细胞样、梭形细胞形态。我们的研究结果证明了基质特性和力学刺激对肌腱分化的重要性。这些结果还证明了BSMFSs的多功能性以及hiPSC - MSCs在肌腱和韧带组织工程中的潜力。（C）2014爱思唯尔有限公司。保留所有权利。
Tendon and ligament (T/L) engineering is a growing area of research with potential to address the inadequacies of current T/L defect treatments. Our group previously developed braided submicron fibrous scaffolds (BSMFSs) and demonstrated the viability of BSMFSs for T/L tissue engineering. The objective of this study was to investigate the effect of fiber chemistry and braiding angle on BSMFS mechanical properties and in turn, tenogenic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) seeded on BSMFSs subjected to cyclic tensile stimulation in the absence of tenogenic medium. By varying fiber chemistry and/or braiding angle, BSMFSs with a range of mechanical properties were produced. We found that fiber chemistry dictated cell adhesion while braiding angle dictated the tissue-specific lineage commitment of hiPSC-MSCs. Scaffolds braided with large angles better supported hiPSC-MSC tenogenic differentiation as evidenced by the production of T/L-associated markers, downregulation of osteogenic markers, and expression of fibroblast-like, spindle cell morphology compared to scaffolds braided with small angles. Our results demonstrate the importance of substrate properties and mechanical stimulation on tenogenic differentiation. These results also demonstrate the versatility of BSMFSs and the potential of hiPSC-MSCs for T/L tissue engineering. (C) 2014 Elsevier Ltd. All rights reserved.