Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel.
Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel.
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DOI：
10.22203/ecm.v019a08
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发表时间：
2010-02-26
影响因子：
3.1
通讯作者：
Mauck RL
中科院分区：
文献类型：
--
作者：
Huang AH;Farrell MJ;Kim M;Mauck RL
间充质干细胞（MSCs）是软骨组织工程中一种有吸引力的细胞来源，因为它们在三维培养系统中具有软骨形成的能力。机械力在调节软骨发育和间充质干细胞软骨形成基因表达方面都起着重要作用，然而，机械刺激尚未能提高工程构建体的力学性能。在这项研究中，我们对接种间充质干细胞的构建体施加长期动态压缩，并评估预培养时间、加载方案的变化以及加载过程中是否包含转化生长因子 -β3会影响功能结果和这些表型转变。在软骨形成之前开始加载会降低功能成熟度，尽管软骨形成基因表达增加。相反，在软骨形成和基质构建之后开始加载进一步提高了基于间充质干细胞构建体的力学性能，但只有在维持转化生长因子 -β3水平且在特定加载参数下才会如此。尽管动态压缩不影响基质数量，但通过组织学和傅里叶变换红外成像系统（FT - IRIS）分析评估，基质分布在微观（细胞周围）和宏观（构建体范围）尺度上都有显著改善。此外，全基因组表达谱分析显示，动态加载使分子图谱发生显著变化。这些结果首次表明，在足够的软骨诱导期之后开始动态压缩加载，并持续暴露于转化生长因子 -β，可增强基质分布和接种间充质干细胞构建体的力学性能。
Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering given their ability to undergo chondrogenesis in 3D culture systems. Mechanical forces play an important role in regulating both cartilage development and MSC chondrogenic gene expression, however, mechanical stimulation has yet to enhance the mechanical properties of engineered constructs. In this study, we applied long-term dynamic compression to MSC-seeded constructs and assessed whether varying pre-culture duration, loading regimens and inclusion of TGF-β3 during loading would influence functional outcomes and these phenotypic transitions. Loading initiated before chondrogenesis decreased functional maturation, although chondrogenic gene expression increased. In contrast, loading initiated after chondrogenesis and matrix elaboration further improved the mechanical properties of MSC-based constructs, but only when TGF-β3 levels were maintained and under specific loading parameters. Although matrix quantity was not affected by dynamic compression, matrix distribution, assessed histologically and by FT-IRIS analysis, was significantly improved on the micro- (pericellular) and macro- (construct expanse) scales. Further, whole genome expression profiling revealed marked shifts in the molecular topography with dynamic loading. These results demonstrate, for the first time, that dynamic compressive loading initiated after a sufficient period of chondro-induction and with sustained TGF-β exposure enhances matrix distribution and the mechanical properties of MSC-seeded constructs.
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影响因子：
2.4
作者：
Albro, Michael B.;Chahine, Nadeen O.;Li, Roland;Yeager, Keith;Hung, Clark T.;Ateshian, Gerard A.
通讯作者：
Ateshian, Gerard A.
影响因子：
2.4
作者：
Huang AH;Farrell MJ;Mauck RL
通讯作者：
Mauck RL
影响因子：
14
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通讯作者：
Burdick, Jason A.
影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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