Mohanraj Bhavana, Huang Alice H, Yeger-McKeever Meira J, Schmidt Megan J, Dodge George R, Mauck Robert L
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
J Orthop Res. 2018 Nov;36(11):2901-2910. doi: 10.1002/jor.24061. Epub 2018 Jul 13.
Tissue engineering is a promising approach for the repair of articular cartilage defects, with engineered constructs emerging that match native tissue properties. However, the inflammatory environment of the damaged joint might compromise outcomes, and this may be impacted by the choice of cell source in terms of their ability to operate anabolically in an inflamed environment. Here, we compared the response of engineered cartilage derived from native chondrocytes and mesenchymal stem cells (MSCs) to challenge by TNFα and IL-1β in order to determine if either cell type possessed an inherent advantage. Compositional (extracellular matrix) and functional (mechanical) characteristics, as well as the release of catabolic mediators (matrix metalloproteinases [MMPs], nitric oxide [NO]) were assessed to determine cell- and tissue-level changes following exposure to IL-1β or TNF-α. Results demonstrated that MSC-derived constructs were more sensitive to inflammatory mediators than chondrocyte-derived constructs, exhibiting a greater loss of proteoglycans and functional properties at lower cytokine concentrations. While MSCs and chondrocytes both have the capacity to form functional engineered cartilage in vitro, this study suggests that the presence of an inflammatory environment is more likely to impair the in vivo success of MSC-derived cartilage repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2901-2910, 2018.
组织工程是修复关节软骨缺损的一种很有前景的方法，出现了一些工程构建体，其性能与天然组织相匹配。然而，受损关节的炎症环境可能会影响治疗效果，而这可能会受到细胞来源选择的影响，因为不同细胞来源在炎症环境中进行合成代谢的能力有所不同。在此，我们比较了源自天然软骨细胞和间充质干细胞（MSC）的工程软骨对TNFα和IL-1β刺激的反应，以确定这两种细胞类型是否具有内在优势。我们评估了其组成（细胞外基质）和功能（力学）特性，以及分解代谢介质（基质金属蛋白酶[MMPs]、一氧化氮[NO]）的释放情况，以确定暴露于IL-1β或TNF-α后细胞和组织水平的变化。结果表明，与软骨细胞来源的构建体相比，MSC来源的构建体对炎症介质更敏感，在较低细胞因子浓度下就表现出蛋白聚糖和功能特性的更大损失。虽然MSC和软骨细胞在体外都有能力形成功能性工程软骨，但本研究表明，炎症环境的存在更有可能损害MSC来源的软骨修复在体内的成功。© 2018骨科学研究协会。由威利期刊公司出版。《矫形外科学研究杂志》36:2901 - 2910，2018年。
