Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China.
Department of Orthopedics Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou City, Zhejiang Province, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou City, Zhejiang Province, PR China; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou City, Zhejiang Province, PR China.
Biomaterials. 2022 Apr;283:121463. doi: 10.1016/j.biomaterials.2022.121463. Epub 2022 Mar 11.
Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for repairing degenerated intervertebral discs through multiple means, including: i. Secretion of bioactive factors to regulate inflammation and, ii. The potential to differentiate into nucleus pulposus (NP)-like cells, which can integrate into host tissues. However, the differentiation ability of ADSCs to NP-like cells is limited, which emphasizes on the need for alternative approaches to regulate cell differentiations. Given that cell functions are influenced by interactions between the extracellular matrix (ECM) and cells, we hypothesize that cell surface modification promotes ADSCs adhesion and differentiation towards NP-like cells. In this study, cell surfaces of ADSCs were functionalized with unnatural sialic acid via metabolic glycoengineering. Subsequently, adhesion abilities of modified cells to three main ECM (laminin, collagen and fibronectin) were compared. The adhesion assay revealed that glycoengineered ADSCs had the highest affinity for collagen, compared to laminin and fibronectin. Moreover, cultures with collagen coated plates enhanced the differentiation of glycoengineered ADSCs to NP-like cells. Metabolic glycoengineering prolonged ADSCs viability. The glycoengineered ADSCs increased the height and elasticity of intervertebral discs, as well as the water content and ECM volumes of nucleus pulposus. In conclusion, metabolic glycoengineering of cell surfaces has a significant role in modulating cell biological functions and promoting NP tissue repair.
脂肪间充质干细胞（ADSCs）通过多种途径有望成为修复退化的椎间盘的候选者，包括：i. 分泌生物活性因子以调节炎症，和 ii. 向类似于髓核（NP）的细胞分化的潜力，这些细胞可以整合到宿主组织中。然而，ADSCs 向 NP 样细胞的分化能力有限，这强调了需要替代方法来调节细胞分化。鉴于细胞功能受到细胞外基质（ECM）与细胞之间相互作用的影响，我们假设细胞表面修饰可促进 ADSCs 向 NP 样细胞的黏附和分化。在这项研究中，通过代谢糖基工程将非天然唾液酸功能化到 ADSCs 的细胞表面上。随后，比较了修饰细胞与三种主要 ECM（层粘连蛋白、胶原蛋白和纤连蛋白）的黏附能力。黏附实验表明，与层粘连蛋白和纤连蛋白相比，糖基化修饰的 ADSCs 对胶原蛋白具有最高的亲和力。此外，在涂有胶原蛋白的培养板上培养可增强糖基化修饰的 ADSCs 向 NP 样细胞的分化。代谢糖基工程延长了 ADSCs 的活力。糖基化修饰的 ADSCs 增加了椎间盘的高度和弹性，以及核髓的含水量和 ECM 体积。总之，细胞表面的代谢糖基工程在调节细胞生物学功能和促进 NP 组织修复方面具有重要作用。
