Gene expression modulation in TGF-β3-mediated rabbit bone marrow stem cells using electrospun scaffolds of various stiffness.
Gene expression modulation in TGF-β3-mediated rabbit bone marrow stem cells using electrospun scaffolds of various stiffness.
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DOI：
10.1111/jcmm.12533
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发表时间：
2015-07
影响因子：
5.3
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Guo Q;Liu C;Li J;Zhu C;Yang H;Li B
组织工程是近年来发展起来的一种有前途的纤维环再生方法。然而，由于AF组织的异质性，选择可以容易地分化为各个区域的AF细胞的理想细胞来源仍然具有挑战性。本研究旨在探讨转化生长因子-β3介导的骨髓干细胞（tBMSCs）用于组织工程化房颤的可行性。由于干细胞的分化显著依赖于基底的刚度，我们从一系列可生物降解的聚（醚碳酸酯氨基甲酸酯）-脲（PECUU）材料制造纳米纤维支架，其弹性模量接近天然AF组织。我们在PECUU支架上培养tBMSCs，并将其基因表达谱与新鉴定的AF组织特异性干细胞AF衍生干细胞（AFSC）进行比较。正如预测的那样，在tBMSC和AFSC中胶原-I的表达随着支架刚度的增加而增加，而胶原-II和聚集蛋白聚糖基因的表达显示出相反的趋势。有趣的是，无论支架刚度如何，PECUU支架上的tBMSC中胶原蛋白-I、胶原蛋白-II和聚集蛋白聚糖基因的表达始终高于AFSC中的表达。此外，tBMSC和AFSC的细胞牵引力（CTF）随着支架刚度逐渐降低，这与天然AF组织的细胞从内部到外部区域的CTF变化相似。总之，这项研究的结果表明，tBMSCs有很强的倾向，分化成各种类型的AF细胞，并提出了类似于AFSC的基因表达谱，从而建立了一个理论基础，在AF组织工程中使用tBMSCs。
Tissue engineering has recently evolved into a promising approach for annulus fibrosus (AF) regeneration. However, selection of an ideal cell source, which can be readily differentiated into AF cells of various regions, remains challenging because of the heterogeneity of AF tissue. In this study, we set out to explore the feasibility of using transforming growth factor-β3-mediated bone marrow stem cells (tBMSCs) for AF tissue engineering. Since the differentiation of stem cells significantly relies on the stiffness of substrate, we fabricated nanofibrous scaffolds from a series of biodegradable poly(ether carbonate urethane)-urea (PECUU) materials whose elastic modulus approximated that of native AF tissue. We cultured tBMSCs on PECUU scaffolds and compared their gene expression profile to AF-derived stem cells (AFSCs), the newly identified AF tissue-specific stem cells. As predicted, the expression of collagen-I in both tBMSCs and AFSCs increased with scaffold stiffness, whereas the expression of collagen-II and aggrecan genes showed an opposite trend. Interestingly, the expression of collagen-I, collagen-II and aggrecan genes in tBMSCs on PECUU scaffolds were consistently higher than those in AFSCs regardless of scaffold stiffness. In addition, the cell traction forces (CTFs) of both tBMSCs and AFSCs gradually decreased with scaffold stiffness, which is similar to the CTF change of cells from inner to outer regions of native AF tissue. Together, findings from this study indicate that tBMSCs had strong tendency to differentiate into various types of AF cells and presented gene expression profiles similar to AFSCs, thereby establishing a rationale for the use of tBMSCs in AF tissue engineering.