Alteration of cellular metabolism by consecutive fed-batch cultures of mammalian cells

The metabolism of myeloma cells was altered to reduce lactate production in consecutive fed-batch cultures. The glucose concentration was maintained a t low levels (0.28-0.55 mM) by employing a dynamic nutrient feeding method based on on-line measurement of the oxygen uptake rate (OUR) to estimate th e metabolic demand of the cells, This strategy has been previously reported to be applied to cultures of hybridoma cells, in which the production of l actate was significantly reduced by thus maintaining the glucose concentrat ion at low levels. However, for this cell line, a single fed-batch culture was not sufficient to alter the cellular metabolism, even at a glucose conc entration of 0.28 mM. Two consecutive fed-batch cultures were employed to e nsure that the cells were cultivated under a low glucose concentration for a sufficiently prolonged period of time to allow a switch of the cellular m etabolism from a glycolytic (high lactate production) to oxidative (low lac tate production) state.