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
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)