Advances in serum-free media for CHO cells: From traditional serum substitutes to microbial-derived substances

IF 3.2 3区生物学 Q2 BIOCHEMICAL RESEARCH METHODS

Biotechnology Journal Pub Date : 2024-06-21 DOI:10.1002/biot.202400251

Mingcan Zhang, Xinyu Zhao, Ying Li, Qinghua Ye, Yuwei Wu, Qinya Niu, Ying Zhang, Guanghan Fan, Tianxiang Chen, Jiarui Xia, Qingping Wu

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Abstract

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.

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CHO 细胞无血清培养基的进展：从传统血清替代品到微生物衍生物质

中国仓鼠卵巢（CHO）细胞是一种类似上皮细胞的细胞，可产生具有与人类糖基化相似的翻译后修饰的蛋白质。它被广泛用于生产重组治疗蛋白和单克隆抗体。培养 CHO 细胞通常需要添加一定比例的胎牛血清（FBS），以维持细胞增殖和传代。然而，血清的特点是成分复杂、批次间可变性大、成本高以及存在支原体和病毒等外源污染物的潜在风险，从而影响合成蛋白质的纯度和安全性。因此，为基于 CHO 的蛋白质生物制造寻找血清替代品和开发无血清培养基意义重大。本综述系统总结了 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等血清替代品的发展趋势，阐明了这些替代品提高 CHO 细胞培养性能和重组蛋白产量的机理，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。

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来源期刊

Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

8.90

自引率

2.10%

发文量

123

审稿时长

1.5 months

期刊介绍： Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.