Coculture of Human Mesenchymal Stem Cells and Articular Chondrocytes Reduces Hypertrophy and Enhances Functional Properties of Engineered Cartilage
Coculture of Human Mesenchymal Stem Cells and Articular Chondrocytes Reduces Hypertrophy and Enhances Functional Properties of Engineered Cartilage
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DOI：
10.1089/ten.tea.2010.0531
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发表时间：
2011-04-01
影响因子：
4.1
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
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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;然而，仅使用MSC来概括天然关节软骨的功能特性仍然是一个挑战。此外，MSC在软骨形成诱导下可能表现出肥大表型，导致异位移植后钙化。考虑到这一点，本研究的目的是评估软骨细胞加入到MSC培养物中是否影响组织工程软骨和MSC肥大在透明质酸水凝胶中培养时的特性。混合细胞群（比例为4：1的人MSC和人软骨细胞）包封在水凝胶中，并且表现出比仅接种MSC或软骨细胞的构建体显著更高的杨氏模量、动态模量、糖胺聚糖水平和胶原含量。此外，胶原蛋白X的沉积，MSC肥大的标志物，是显着低于在共培养的结构比单独与MSC接种的结构。当MSC和软骨细胞在不同的凝胶中培养时，但在相同的威尔斯孔中，工程组织的生物力学和生物化学性质没有改善，这意味着紧密接近是必不可少的。这种方法可用于改善由MSC接种的水凝胶形成的工程化软骨的性质并防止其钙化，同时添加较低比例的软骨细胞，从而改善临床结果。
Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair; however, it still remains a challenge to recapitulate the functional properties of native articular cartilage using only MSCs. Additionally, MSCs may exhibit a hypertrophic phenotype under chondrogenic induction, resulting in calcification after ectopic transplantation. With this in mind, the objective of this study was to assess whether the addition of chondrocytes to MSC cultures influences the properties of tissue-engineered cartilage and MSC hypertrophy when cultured in hyaluronic acid hydrogels. Mixed cell populations (human MSCs and human chondrocytes at a ratio of 4:1) were encapsulated in the hydrogels and exhibited significantly higher Young's moduli, dynamic moduli, glycosaminoglycan levels, and collagen content than did constructs seeded with only MSCs or chondrocytes. Furthermore, the deposition of collagen X, a marker of MSC hypertrophy, was significantly lower in the coculture constructs than in the constructs seeded with MSCs alone. When MSCs and chondrocytes were cultured in distinct gels, but in the same wells, there was no improvement in biomechanical and biochemical properties of the engineered tissue, implying that a close proximity is essential. This approach can be used to improve the properties and prevent calcification of engineered cartilage formed from MSC-seeded hydrogels with the addition of lower fractions of chondrocytes, leading to improved clinical outcomes.