Modulation of the gene expression of annulus fibrosus-derived stem cells using poly(ether carbonate urethane)urea scaffolds of tunable elasticity.
Modulation of the gene expression of annulus fibrosus-derived stem cells using poly(ether carbonate urethane)urea scaffolds of tunable elasticity.
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弹性可调的聚醚碳酸酯脲支架对纤维环衍生干细胞基因表达的调控。
DOI：
10.1016/j.actbio.2015.09.039
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发表时间：
2016
影响因子：
9.7
通讯作者：
Caihong Zhu;Jun Li;Chen Liu;Pinghui Zhou;Huilin Yang;Bin Li
中科院分区：
文献类型：
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作者：
Caihong Zhu;Jun Li;Chen Liu;Pinghui Zhou;Huilin Yang;Bin Li
纤维环（AF）损伤通常会导致椎间盘（IVD）严重恶化。虽然组织工程最近已发展成为一种有前景的房颤再生方法，但由于房颤组织的细胞、生化和机械异质性，它仍然具有挑战性。在本研究中，我们探索了利用房颤衍生干细胞（AFSC）实现房颤组织工程细胞的多样化分化。由于干细胞的分化很大程度上依赖于基质的弹性，因此我们合成了一系列可生物降解的聚醚碳酸酯尿烷（PECUU）材料，其弹性接近天然AF组织的弹性。当AFSCs在电纺PECUU纤维支架上培养时，细胞中胶原蛋白I的基因表达随着支架材料的弹性而增加，而胶原蛋白II和聚集蛋白聚糖基因的表达则呈现相反的趋势。在蛋白质水平上，随着基质弹性的增加，I型胶原蛋白的含量逐渐增加，而II型胶原蛋白和GAG的含量则逐渐减少。此外，AFSC的细胞牵引力（CTF）随着支架弹性的增加而逐渐降低。 AFSC 的这种基质弹性依赖性变化类似于细胞的遗传、生化和生物力学特征从天然 AF 组织的内部区域到外部区域的逐渐转变。总之，本研究的结果表明，AFSCs 根据基质弹性，具有强烈分化为各种类型 AF 样细胞的倾向，从而为 AFSCs 的组织工程应用提供了坚实的基础。 意义声明 修复椎间盘（IVD）纤维环（AF）对于椎间盘退变疾病的治疗至关重要，但由于 AF 组织的显着异质性，仍然具有挑战性。此前，我们已经鉴定出兔房颤衍生干细胞（AFSC），它们具有房颤组织特异性，有望实现房颤再生。在本研究中，我们合成了一系列具有不同弹性（或刚度）的聚（醚碳酸酯聚氨酯）脲，并探索了使用电纺 PECUU 支架诱导 AFSC 分化的潜力。这项工作首次发现 AFSC 能够仅由于支架材料的弹性而呈现不同的基因表达模式。因此，我们的研究结果将有助于补充当前关于 AF 组织再生的知识，并可能使来自科学、工程和临床环境、其工作涉及 IVD 生物学和组织工程的多元化读者受益。
Annulus fibrosus (AF) injuries commonly lead to substantial deterioration of the intervertebral disc (IVD). While tissue engineering has recently evolved into a promising approach for AF regeneration, it remains challenging due to the cellular, biochemical, and mechanical heterogeneity of AF tissue. In this study, we explored the use of AF-derived stem cells (AFSCs) to achieve diversified differentiation of cells for AF tissue engineering. Since the differentiation of stem cells relies significantly on the elasticity of the substrate, we synthesized a series of biodegradable poly(ether carbonate urethane)urea (PECUU) materials whose elasticity approximated that of native AF tissue. When AFSCs were cultured on electrospun PECUU fibrous scaffolds, the gene expression of collagen-I in the cells increased with the elasticity of scaffold material, whereas the expression of collagen-II and aggrecan genes showed an opposite trend. At the protein level, the content of collagen-I gradually increased with substrate elasticity, while collagen-II and GAG contents decreased. In addition, the cell traction forces (CTFs) of AFSCs gradually decreased with scaffold elasticity. Such substrate elasticity-dependent changes of AFSCs were similar to the gradual transition in the genetic, biochemical, and biomechanical characteristics of cells from inner to outer regions of native AF tissue. Together, findings from this study indicate that AFSCs, depending on the substrate elasticity, have strong tendencies to differentiate into various types of AF-like cells, thereby providing a solid foundation for the tissue engineering applications of AFSCs.Statement of significanceRepairing the annulus fibrosus (AF) of intervertebral disc (IVD) is critical for the treatment of disc degeneration disease, but remains challenging due to the significant heterogeneity of AF tissue. Previously, we have identified rabbit AF-derived stem cells (AFSCs), which are AF tissue-specific and hold promise for AF regeneration. In this study, we synthesized a series of poly(ether carbonate urethane)ureas of various elasticity (or stiffness) and explored the potential of induced differentiation of AFSCs using electrospun PECUU scaffolds. This work has, for the first time, found that AFSCs are able to present different gene expression patterns simply as a result of the elasticity of scaffold material. Therefore, our findings will help supplement current knowledge of AF tissue regeneration and may benefit a diversified readership from scientific, engineering, and clinical settings whose work involves the biology and tissue engineering of IVD.