EFFECTS OF GLUCOSE AND CO_2 CONCENTRATIONS ON CHO CELL PHYSIOLOGY

摘要

This study investigated the combined effects of glucose and CO_2 on monoclonal antibody producing Chinese Hamster Ovary (CHO) cells in a perfusion reactor operated with a controlled cell specific medium feed rate, pH and osmolality. Under high glucoseconditions, the glucose was mainly converted to lactate, and the lactate yield from glucose was not affected by CO_2 concentrations up to 30%. The growth rate declined as the CO_2 concentration increased to 30%, and the cell specific antibody productivity was almost unchanged. A feed medium change from high (33 mM) to low (6 mM) glucose resulted in <0.1 mM glucose in the culture and, at 7% CO_2, a 26% higher growth rate. As a result of shifting metabolism towards more conversion of pyruvate to CO_2, the ratio of lactate to glucose and alanine production were both lowered. Interestingly, when the CO_2 concentration was increased to 20%, limiting glucose resulted in 1.7-fold higher growth rates. However, at 30% CO_2 the beneficial effect of glucose limitation on these CHO cells was lost as the growth rate dropped dramatically to 0.008 h~(-1) and the antibody productivity was lowered by 15%.