Chinese hamster ovary cell performance enhanced by a rational divide-and-conquer strategy for chemically defined medium development

Liu, Yaya; Zhang, Weiyan; Deng, Xiancun; Poon, H. Fai; Liu, Xuping; Tan, Wen‐Song; Zhou, Yan; Fan, Li

doi:10.1016/j.jbiosc.2015.04.016

Cited by 12 publications

(5 citation statements)

References 31 publications

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“…A simplex design was adopted for this experiment since this approach, applied by others, is known to be well‐suited for mixture design (Didier et al, 2007; Jordan et al, 2013; Kim & Lee, 2009; Liu et al, 2015). The design was a simplex‐centroid including the four media (M1–M4), which resulted in 15 mixtures (N1–N15) with three center points (N15–N17), and is presented in Table 3.…”

Section: Resultsmentioning

confidence: 99%

“…Due to the high complexity of media for mammalian cell culture, one‐factor‐at‐a‐time optimization strategy has been found to be ineffective and instead the statistical approach of design of experiments (DoE) is most often adopted to reduce the number of experiments (Ritacco et al, 2018). DoE has been applied to improve the production of mAbs in Chinese hamster ovary (CHO) cell lines by analyzing the effect of components with a response surface methodology and identifying their optimum levels (Liu et al, 2015; Torkashvand et al, 2015). Another experimental approach, namely metabolic profiling, has demonstrated its effectiveness in optimizing mAb production through the design of feed regimes relieving metabolic bottlenecks from nutrient limitations (Kishishita et al, 2015; Sellick et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments

Schwarz

Lee²,

Castan³

et al. 2023

Biotech & Bioengineering

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A novel approach of design of experiment (DoE) is developed for the optimization of key substrates of the culture medium, amino acids, and sugars, by utilizing perfusion microbioreactors with 2 mL working volume, operated in high cell density continuous mode, to explore the design space. A mixture DoE based on a simplex‐centroid is proposed to test multiple medium blends in parallel perfusion runs, where the amino acids concentrations are selected based on the culture behavior in presence of different amino acid mixtures, and using targeted specific consumption rates. An optimized medium is identified with models predicting the culture parameters and product quality attributes (G0 and G1 level N‐glycans) as a function of the medium composition. It is then validated in runs performed in perfusion microbioreactor in comparison with stirred‐tank bioreactors equipped with alternating tangential flow filtration (ATF) or with tangential flow filtration (TFF) for cell separation, showing overall a similar process performance and N‐glycosylation profile of the produced antibody. These results demonstrate that the present development strategy generates a perfusion medium with optimized performance for stable Chinese hamster ovary (CHO) cell cultures operated with very high cell densities of 60 × 106 and 120 × 106 cells/mL and a low cell‐specific perfusion rate of 17 pL/cell/day, which is among the lowest reported and is in line with the framework recently published by the industry.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments

Schwarz

Lee²,

Castan³

et al. 2023

Biotech & Bioengineering

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show abstract

“…Four different mAbs Divide-and-conquer strategy: spent medium analysis, design-expert, and multivariate analysis Glucose, asparagine, glutamine, ferric citrate, vitamin B12, myo-inositol, niacinamide, putrescine 2 HCl, folic acid, and sodium selenite [95] CHO-DG44, CHO DUKX-B11…”

Section: Mechanisms Of Sfm On Cell Growth and Recombinant Protein Pro...mentioning

confidence: 99%

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

Zhang,

Zhao,

et al. 2024

Biotechnology Journal

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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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“…Indeed, detailed media optimizations utilizing DOE have been reported for effective recombinant protein and antibody production processes. We collected DOE investigations evaluating cell yield and/or viability as response variables [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ], or selecting desirable clones [ 96 , 97 ].…”

Section: Cho Cell Expansionmentioning

confidence: 99%

Clever Experimental Designs: Shortcuts for Better iPSC Differentiation

Yasui

Sekine

Taniguchi

2021

Cells

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For practical use of pluripotent stem cells (PSCs) for disease modelling, drug screening, and regenerative medicine, the cell differentiation process needs to be properly refined to generate end products with consistent and high quality. To construct and optimize a robust cell-induction process, a myriad of cell culture conditions should be considered. In contrast to inefficient brute-force screening, statistical design of experiments (DOE) approaches, such as factorial design, orthogonal array design, response surface methodology (RSM), definitive screening design (DSD), and mixture design, enable efficient and strategic screening of conditions in smaller experimental runs through multifactorial screening and/or quantitative modeling. Although DOE has become routinely utilized in the bioengineering and pharmaceutical fields, the imminent need of more detailed cell-lineage specification, complex organoid construction, and a stable supply of qualified cell-derived material requires expedition of DOE utilization in stem cell bioprocessing. This review summarizes DOE-based cell culture optimizations of PSCs, mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), and Chinese hamster ovary (CHO) cells, which guide effective research and development of PSC-derived materials for academic and industrial applications.

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Chinese hamster ovary cell performance enhanced by a rational divide-and-conquer strategy for chemically defined medium development

Cited by 12 publications

References 31 publications

Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments

Optimization of medium with perfusion microbioreactors for high density CHO cell cultures at very low renewal rate aided by design of experiments

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

Clever Experimental Designs: Shortcuts for Better iPSC Differentiation

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