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

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Abstract
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 Unes 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 >70%) and lactate accumulation (decreased by >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.