Kim Ha Na, Whitelock John M, Lord Megan S
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Molecules. 2017 May 15;22(5):806. doi: 10.3390/molecules22050806.
Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity.
肝素和硫酸乙酰肝素是结构相关的碳水化合物，在抗凝、药物递送和再生医学中具有治疗应用。本研究通过在哺乳动物细胞中重组表达丝甘蛋白，探索了不同生物反应器条件对肝素/硫酸乙酰肝素链产生的影响。组织培养瓶和连续搅拌罐反应器促进了装饰有肝素/硫酸乙酰肝素以及硫酸软骨素的丝甘蛋白的产生，而组织培养瓶中的细胞分泌的丝甘蛋白产生了硫酸化程度更高的肝素/硫酸乙酰肝素链。在组织培养瓶中产生的丝甘蛋白能有效结合并传导成纤维细胞生长因子2，这表明该分子除了具有众所周知的抗凝活性外，在药物递送和再生医学应用中也具有实用性。
