National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.
Department of Food Science and Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
Biotechnol J. 2024 Jun;19(6):e2400251. doi: 10.1002/biot.202400251.
The Chinese hamster ovary (CHO) cell is an epithelial-like cell that produces proteins with post-translational modifications similar to human glycosylation. It is widely used in the production of recombinant therapeutic proteins and monoclonal antibodies. Culturing CHO cells typically requires the addition of a certain proportion of fetal bovine serum (FBS) to maintain cell proliferation and passaging. However, serum is characterized by its complex composition, batch-to-batch variability, high cost, and potential risk of exogenous contaminants such as mycoplasma and viruses, which impact the purity and safety of the synthesized proteins. Therefore, search for serum alternatives and development of serum-free media for CHO-based protein biomanufacturing are of great significance. This review systematically summarizes the application advantages of CHO cells and strategies for high-density expression. It highlights the developmental trends of serum substitutes from human platelet lysates to animal-free extracts and microbial-derived substances and elucidates the mechanisms by which these substitutes enhance CHO cell culture performance and recombinant protein production, aiming to provide theoretical guidance for exploring novel serum alternatives and developing serum-free media for CHO cells.
中国仓鼠卵巢（CHO）细胞是一种上皮样细胞，能够对蛋白质进行翻译后修饰，其糖基化模式与人相似。CHO 细胞广泛应用于重组治疗蛋白和单克隆抗体的生产。培养 CHO 细胞通常需要添加一定比例的胎牛血清（FBS）来维持细胞增殖和传代。然而，血清的特点是组成复杂、批次间差异大、成本高，并且存在支原体和病毒等外源污染物的潜在风险，这些因素会影响合成蛋白的纯度和安全性。因此，寻找血清替代品并开发无血清培养基对于基于 CHO 的蛋白生物制造具有重要意义。本综述系统地总结了 CHO 细胞的应用优势和高密度表达策略。重点介绍了从人血小板裂解物到无动物提取物和微生物衍生物质的血清替代品的发展趋势，并阐明了这些替代品如何增强 CHO 细胞培养性能和重组蛋白生产的机制，旨在为探索新型血清替代品和开发 CHO 细胞无血清培养基提供理论指导。
