Enhanced recombinant M-CSF production in CHO cells by glycerol addition: model and validation |
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Authors: | Chi-Hsien Liu Li-Hsin Chen |
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Institution: | (1) Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, 259, Wen-Hwa first Road, Kwei-Shan, Taoyuan, 333, Taiwan |
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Abstract: | Addition of stimulatory chemical such as glycerol was found to increase recombinant protein production in Chinese hamster
ovary (CHO) cells. However, glycerol influenced cell mitosis and reduced cell growth rate. We developed a controlled proliferation
strategy to utilize the stimulation of glycerol on recombinant protein production and mitigate the problem of growth inhibition.
The approach is to apply a two-stage process, where cells are cultured without glycerol for a period of time in order to obtain
enough cell density and then glycerol is added to achieve high specific productivity. In addition, a model for predicting
the profiles of cell proliferation and recombinant protein production was developed and validated. A two-stage process, addition
of 1% glycerol after 1 day of growth, could increase the final production of macrophage-colony stimulating factor (M-CSF)
by 38% compared with the value obtained without addition of glycerol. |
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Keywords: | CHO cells Controlled proliferation Glycerol M-CSF Model Optimization |
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