Dynamic Compressive Loading Enhances Cartilage Matrix Synthesis and Distribution and Suppresses Hypertrophy in hMSC-Laden Hyaluronic Acid Hydrogels
Dynamic Compressive Loading Enhances Cartilage Matrix Synthesis and Distribution and Suppresses Hypertrophy in hMSC-Laden Hyaluronic Acid Hydrogels
复制标题
DOI：
10.1089/ten.tea.2011.0455
复制
发表时间：
2012-04-01
影响因子：
4.1
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
--
作者：
Bian, Liming;Zhai, David Y.;Burdick, Jason A.
间充质干细胞（MSC）被认为是软骨修复的活细胞来源，越来越多的证据表明，机械信号在调节干细胞软骨发生和软骨发育中起着关键作用。在这项研究中，我们研究了动态压缩负荷对软骨形成的影响，软骨特异性基质的产生和分布，以及在长期培养过程中包埋在透明质酸（HA）水凝胶中的人MSC的肥大分化。培养70天后，动态压缩载荷以接种密度依赖性方式增加了HA水凝胶构建体的机械性能以及糖胺聚糖（GAG）和胶原含量。与较高接种密度（6000万MSC/ml）构建体相比，当应用于较低密度（2000万MSC/ml）时，加载对HA水凝胶构建体性质的影响延迟。此外，加载促进了具有两种接种密度的HA水凝胶中软骨基质的更均匀的空间分布，导致与自由溶胀构建体相比显著改善的机械性能。使用先前开发的体外肥大模型，动态压缩载荷也显示出显着降低人MSC的肥大标志物的表达，并抑制MSC接种的HA水凝胶的钙化程度。这项研究的结果突出了机械负荷在基于干细胞的软骨修复治疗中改善新软骨特性和潜在维持软骨表型的重要性。
Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair, and there is growing evidence that mechanical signals play a critical role in the regulation of stem cell chondrogenesis and in cartilage development. In this study we investigated the effect of dynamic compressive loading on chondrogenesis, the production and distribution of cartilage specific matrix, and the hypertrophic differentiation of human MSCs encapsulated in hyaluronic acid (HA) hydrogels during long term culture. After 70 days of culture, dynamic compressive loading increased the mechanical properties, as well as the glycosaminoglycan (GAG) and collagen contents of HA hydrogel constructs in a seeding density dependent manner. The impact of loading on HA hydrogel construct properties was delayed when applied to lower density (20 million MSCs/ml) compared to higher seeding density (60 million MSCs/ml) constructs. Furthermore, loading promoted a more uniform spatial distribution of cartilage matrix in HA hydrogels with both seeding densities, leading to significantly improved mechanical properties as compared to free swelling constructs. Using a previously developed in vitro hypertrophy model, dynamic compressive loading was also shown to significantly reduce the expression of hypertrophic markers by human MSCs and to suppress the degree of calcification in MSC-seeded HA hydrogels. Findings from this study highlight the importance of mechanical loading in stem cell based therapy for cartilage repair in improving neocartilage properties and in potentially maintaining the cartilage phenotype.