Enhancement of nucleus pulposus repair by glycoengineered adipose-derived mesenchymal cells.
Enhancement of nucleus pulposus repair by glycoengineered adipose-derived mesenchymal cells.
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DOI：
10.1016/j.biomaterials.2022.121463
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发表时间：
2022-03
期刊：
影响因子：
14
通讯作者：
Liwei Ying;Cheng-zhen Liang;Yujie Zhang;Jingkai Wang;Chenggui Wang;Kaishun Xia;Kesi Shi;Chao Yu
中科院分区：
文献类型：
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作者：
Liwei Ying;Cheng-zhen Liang;Yujie Zhang;Jingkai Wang;Chenggui Wang;Kaishun Xia;Kesi Shi;Chao Yu
脂肪源性间充质干细胞(ADSCs)可通过多种途径修复退变的椎间盘，包括：1.分泌生物活性因子调节炎症；2.分化为髓核(NP)样细胞的潜力，可整合到宿主组织中。然而，ADSCs向NP样细胞分化的能力是有限的，这强调了需要替代的方法来调节细胞分化。鉴于细胞功能受细胞外基质(ECM)和细胞之间相互作用的影响，我们假设细胞表面修饰促进ADSCs向NP样细胞的黏附和分化。在本研究中，通过代谢糖工程，用非天然唾液酸对ADSCs细胞表面进行功能化。随后，比较了修饰细胞与三种主要的细胞外基质(层粘连蛋白、胶原和纤维连接蛋白)的黏附能力。黏附实验显示，与层粘连蛋白和纤维连接蛋白相比，糖工程ADSCs对胶原的亲和力最高。此外，包被胶原的培养板可促进糖工程ADSCs向NP样细胞分化。代谢糖工程延长了ADSCs的存活率。糖工程ADSCs增加了椎间盘的高度和弹性，增加了髓核的含水率和ECM体积。综上所述，细胞表面代谢糖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。
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.