Adaptation to non-ammoniagenic medium and selective substrate feeding lead to enhanced yields in animal cell cultures

Methods for the adaptation of three animal cell lines to media in which glutamine is replaced with either glutamate or 2-oxoglutarate are described. The cell lines differ in their rate of adaptation. The consequences of the adaptation of the McCoy cell line to a glutamate-based medium was measured in terms of: cell yield (increased by 17%), ammonia accumulation (reduced by 70%), glucose consumption (decreased by greater than 70%) and lactate accumulation (decreased by greater than 75%). The value of such adaptation and concomitant changes in energy metabolism lies in the potential for increased cell yields. Batch feeding of adapted cells in a microcarrier culture with a cocktail of glucose and amino acids resulted in increases in cell yields of 80% compared to unfed controls.