最佳蓝光照射:一种提高中国仓鼠卵巢细胞特异性生产力的方法

IF 3.9 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Applied Microbiology and Biotechnology Pub Date : 2024-12-05 DOI:10.1007/s00253-024-13363-4
Stefanie Föller, Niklas Regett, Levin Lataster, Gerald Radziwill, Ralf Takors
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引用次数: 0

摘要

利用哺乳动物细胞进行生物制药生产工艺的研究,其目标是不断提高细胞特异性生产效率,从而优化生物反应器的总生产效率。目前的技术如pH值、温度和渗透压的改变需要对培养基进行修改,而在重组产生细胞中使用光遗传开关可能是一种很有前途的无接触替代方法。然而,光基因工程细胞的正确应用需要对尚未包含光基因开关的细胞的基本细胞反应有详细的了解。目前还缺乏理想的光照,以使相关方法的最佳使用成为可能。因此,目前的研究开始寻找暴露于蓝色LED光下的中国仓鼠卵巢(CHO)细胞产生IgG1的最佳条件。使用酶联免疫吸附法分析生长特性、细胞特异性生产力以及使用流式细胞术分析细胞周期分布。虽然过度的强光照射会对生长产生不利影响,但可以用抗氧化剂来补偿,但在最佳的强光照射下,细胞特异性生产力惊人地提高了57%。光照72h后,细胞周期G1期细胞数量增加。这一结果为提高哺乳动物细胞的生物制药生产力提供了一种有希望的新方法,只需适当的光照,而无需进一步的光基因工程。•蓝色LED光阻碍CHO DP-12细胞的生长•抗氧化剂在一定程度上保护免受蓝光影响•蓝色LED光照明提高细胞特异性生产力
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Optimum blue light exposure: a means to increase cell-specific productivity in Chinese hamster ovary cells

Research for biopharmaceutical production processes with mammalian cells steadily aims to enhance the cell-specific productivity as a means for optimizing total productivities of bioreactors. Whereas current technologies such as pH, temperature, and osmolality shift require modifications of the cultivation medium, the use of optogenetic switches in recombinant producer cells might be a promising contact-free alternative. However, the proper application of optogenetically engineered cells requires a detailed understanding of basic cellular responses of cells that do not yet contain the optogenetic switches. The knowhow of ideal light exposure to enable the optimum use of related approaches is missing so far. Consequently, the current study set out to find optimum conditions for IgG1 producing Chinese hamster ovary (CHO) cells which were exposed to blue LED light. Growth characteristics, cell-specific productivity using enzyme-linked immunosorbent assay, as well as cell cycle distribution using flow cytometry were analyzed. Whereas too harsh light exposure causes detrimental growth effects that could be compensated with antioxidants, a surprising boost of cell-specific productivity by 57% occurred at optimum high light doses. The increase coincided with an increased number of cells in the G1 phase of the cell cycle after 72 h of illumination. The results present a promising new approach to boost biopharmaceutical productivity of mammalian cells simply by proper light exposure without any further optogenetic engineering.

• Blue LED light hinders growth in CHO DP-12 cells

• Antioxidants protect to a certain degree from blue light effects

• Illumination with blue LED light raises cell-specific productivity

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来源期刊
Applied Microbiology and Biotechnology
Applied Microbiology and Biotechnology 工程技术-生物工程与应用微生物
CiteScore
10.00
自引率
4.00%
发文量
535
审稿时长
2 months
期刊介绍: Applied Microbiology and Biotechnology focusses on prokaryotic or eukaryotic cells, relevant enzymes and proteins; applied genetics and molecular biotechnology; genomics and proteomics; applied microbial and cell physiology; environmental biotechnology; process and products and more. The journal welcomes full-length papers and mini-reviews of new and emerging products, processes and technologies.
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