Ectoine enhances recombinant antibody production in Chinese hamster ovary cells by promoting cell cycle arrest

IF 4.5 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS New biotechnology Pub Date : 2024-06-28 DOI:10.1016/j.nbt.2024.06.006

Salinthip Jarusintanakorn , Enrico Mastrobattista , Montarop Yamabhai

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Abstract

Chinese hamster ovary (CHO) cells represent the most preferential host cell system for therapeutic monoclonal antibody (mAb) production. Enhancing mAb production in CHO cells can be achieved by adding chemical compounds that regulate the cell cycle and cell survival pathways. This study investigated the impact of ectoine supplementation on mAb production in CHO cells. The results showed that adding ectoine at a concentration of 100 mM on the 3^rd day of cultivation improved mAb production by improving cell viability and extending the culture duration. RNA sequencing analysis revealed differentially expressed genes associated with cell cycle regulation, cell proliferation, and cellular homeostasis, in particular promotion of cell cycle arrest, which was then confirmed by flow cytometry analysis. Ectoine-treated CHO cells exhibited an increase in the number of cells in the G0/G1 phase. In addition, the cell diameter was also increased. These findings support the hypothesis that ectoine enhances mAb production in CHO cells through mechanisms involving cell cycle arrest and cellular homeostasis. Overall, this study highlights the potential of ectoine as a promising supplementation strategy to enhance mAb production not only in CHO cells but also in other cell lines.

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辛胺通过促进细胞周期停滞来提高中国仓鼠卵巢细胞重组抗体的产生。

中国仓鼠卵巢（CHO）细胞是生产治疗性单克隆抗体（mAb）最理想的宿主细胞系统。通过添加调节细胞周期和细胞存活途径的化合物，可以提高 CHO 细胞的 mAb 产量。本研究调查了在 CHO 细胞中添加埃克替丁对 mAb 生产的影响。结果表明，在培养的第三天添加浓度为 100mM 的埃克托因可提高细胞活力并延长培养时间，从而提高 mAb 的产量。RNA测序分析发现了与细胞周期调控、细胞增殖和细胞稳态有关的差异表达基因，尤其是促进细胞周期停滞的基因，流式细胞仪分析证实了这一点。经依克托品处理的 CHO 细胞显示出 G0/G1 期细胞数量的增加。此外，细胞直径也有所增加。这些发现支持了这样的假设：埃克托因通过涉及细胞周期停滞和细胞平衡的机制来提高 CHO 细胞的 mAb 产量。总之，本研究强调了伊可新作为一种有前途的补充策略，不仅能提高 CHO 细胞的 mAb 产量，还能提高其他细胞系的 mAb 产量。

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来源期刊

New biotechnology 生物-生化研究方法

CiteScore

11.40

自引率

1.90%

发文量

审稿时长

1 months

期刊介绍： New Biotechnology is the official journal of the European Federation of Biotechnology (EFB) and is published bimonthly. It covers both the science of biotechnology and its surrounding political, business and financial milieu. The journal publishes peer-reviewed basic research papers, authoritative reviews, feature articles and opinions in all areas of biotechnology. It reflects the full diversity of current biotechnology science, particularly those advances in research and practice that open opportunities for exploitation of knowledge, commercially or otherwise, together with news, discussion and comment on broader issues of general interest and concern. The outlook is fully international. The scope of the journal includes the research, industrial and commercial aspects of biotechnology, in areas such as: Healthcare and Pharmaceuticals; Food and Agriculture; Biofuels; Genetic Engineering and Molecular Biology; Genomics and Synthetic Biology; Nanotechnology; Environment and Biodiversity; Biocatalysis; Bioremediation; Process engineering.