Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan.
J Biosci Bioeng. 2011 Feb;111(2):226-31. doi: 10.1016/j.jbiosc.2010.10.002. Epub 2010 Oct 29.
Chondroitin sulfate C (CSC) is a kind of glycosaminoglycans (GAGs) with molecular weights of 10,000 to 50,000 Da and a high charge density. GAGs are major components in extracellular matrix (ECM), which play important role in the regulation of cell proliferation, migration, and differentiation. In this study, we studied the effects of chondroitin sulfate C (CSC) on the differentiation of human mesenchymal stem cells (MSCs) toward the chondrocyte lineage. The MSCs were either cultured on type II collagen (COL II) scaffolds with high molecular weight CSC addition in the medium (free CSC) or with free oligosaccharide CSC. Special attention was given to the effects of MSCs cultured on CSC cross-linked type II scaffolds (cross-linked CSC). According to the analysis of histology stain, gene expression, and ECM secretion, our results showed that MSCs cultured with free CSC, free oligosaccharides CSC, and on the cross-linked CSC scaffolds all would be induced into chondrocytes. Moreover, free oligosaccharide CSC present in the microenvironment could significantly up-regulate MSC chondrogenesis gene expression and stimulate cartilage ECM accumulation more than free CSC with high molecular weight after 3-week induction. Importantly, cross-linked CSC had the most excellent effects on the MSC chondrogenesis. Thus, we believed that cross-linked CSC in the scaffold would play the similar roles with free oligosaccharide CSC in the medium. Cross-linked CSC would be a potential candidate for cartilage repair in the cell therapy and tissue engineering.
硫酸软骨素 C(CSC)是一种糖胺聚糖(GAGs),分子量为 10,000 至 50,000 Da,电荷密度高。GAGs 是细胞外基质(ECM)的主要成分,在调节细胞增殖、迁移和分化方面发挥着重要作用。在这项研究中,我们研究了硫酸软骨素 C(CSC)对人骨髓间充质干细胞(MSCs)向软骨细胞谱系分化的影响。MSCs 要么在高相对分子质量 CSC 存在于培养基中的 II 型胶原(COL II)支架上培养(游离 CSC),要么在游离寡糖 CSC 存在的情况下培养。特别关注的是在交联的 II 型支架上培养的 MSCs(交联 CSC)的影响。根据组织学染色、基因表达和 ECM 分泌的分析,我们的结果表明,在游离 CSC、游离寡糖 CSC 和交联 CSC 支架上培养的 MSCs 都会被诱导为软骨细胞。此外,微环境中的游离寡糖 CSC 可以显著上调 MSC 软骨生成基因表达,并在 3 周诱导后刺激软骨 ECM 的积累,比高相对分子质量的游离 CSC 更显著。重要的是,交联 CSC 对 MSC 软骨生成的影响最为显著。因此,我们认为支架中的交联 CSC 将发挥与培养基中游离寡糖 CSC 类似的作用。交联 CSC 可能是细胞治疗和组织工程中软骨修复的潜在候选物。