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二氧化碳分压和渗透压升高对CHO细胞维持期生长、代谢和产物表达的影响

王晨 汪嘉琪 赵亮 范里 刘旭平 陈敏 张理想 谭文松

生物技术通报2018,Vol.34Issue(3):217-224,8.
生物技术通报2018,Vol.34Issue(3):217-224,8.DOI:10.13560/j.cnki.biotech.bull.1985.2017-0749

二氧化碳分压和渗透压升高对CHO细胞维持期生长、代谢和产物表达的影响

Effects of Raising pCO2 and Osmolality on the Growth, Metabolism and Productivity of CHO Cells at Maintenance Phase

王晨 1汪嘉琪 1赵亮 1范里 2刘旭平 1陈敏 2张理想 1谭文松2

作者信息

  • 1. 华东理工大学生物反应器工程国家重点实验室,上海200237
  • 2. 上海倍谙基生物科技有限公司,上海200237
  • 折叠

摘要

Abstract

The aim of this study is to understand the effects of pCO2 and osmolality on the monoclonal antibody (mAb) production during the maintenance phase of Chinese hamster ovary (CHO) cell cultures.Cell maintenance,metabolism,antibody quantity and quality at different pCO2 and osmolality levels were investigated during cell maintenance.It was found that the raise of pCO2 and osmolality brought negative impacts on final antibody production.The increase of osmolality damaged the cell maintenance,while the increase of pCO2 downregulated the productivity of CHO cells.Through comparing the extracellular and intracellular metabolites,the increase of pCO2 and osmolality resulted in the decrease of carbon source utilization.Besides,on the antibody quality,the increase of osmolality decreased the glycosylation but raised the ratio of neutral charge.Moreover,the increase of pCO2 mainly enhanced the charge heterogeneity but there were no changes on the sugar type distribution of the products.Conclusively,the increase of pCO2 and osmolality during the phase of antibody expression had unfavorable effects on the cell maintenance,both material and energy metabolism,and the expression of product antibody;thus the accumulation of CO2 and osmolality elevation should be avoided as much as possible in order to ensure the normal proceeding of large-scale culture.

关键词

二氧化碳分压/渗透压/CHO细胞/单克隆抗体/代谢

Key words

pCO2/osmolality/CHO cells/monoclonal antibody/metabolism

引用本文复制引用

王晨,汪嘉琪,赵亮,范里,刘旭平,陈敏,张理想,谭文松..二氧化碳分压和渗透压升高对CHO细胞维持期生长、代谢和产物表达的影响[J].生物技术通报,2018,34(3):217-224,8.

基金项目

国家自然科学基金项目(21106045),国家重大专项(2013ZX10004003-003-003) (21106045)

生物技术通报

OA北大核心CSCDCSTPCD

1002-5464

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