Partial Replacement of Chemically Defined Media with Plant-Derived Protein Hydrolysates - - BioPharm International


Partial Replacement of Chemically Defined Media with Plant-Derived Protein Hydrolysates

BioPharm International Supplements

Enhanced Cell Performance Attributed to Shift in Metabolism

Figure 3
During the course of these experiments, the levels of glucose, lactate, glutamine, and glutamate in the culture media were monitored. In a majority of our tests, cultures maintained in CDM were subject to a continuous accumulation of lactate throughout the life of the culture, while those supplemented with the hydrolysate experienced a shift in metabolism with respect to the fate of lactate in the late stages of the production runs. This shift occurred when more abundant carbon sources, such as glucose and glutamine, had fallen below certain critical levels or were entirely depleted from the culture medium.6 This may explain, in part, why in most cases hydrolysate-supplemented cultures exhibit extended growth curves and enhanced cell viabilities compared to unsupplemented cultures. In addition, although in this example the shift is seen to a certain degree in the unsupplemented cultures, it is significantly more pronounced in the hydrolysate-supplemented treatments. This ability to efficiently metabolize lactate correlates well with increased target protein production.

Synergistic Effects

Figure 4
The performance benefit provided by any medium supplement is subject to its interaction with other medium components present in the basal formulation, as well as any additional supplements being used. In some instances, a combination of supplements may provide better performance than that observed when supplementing with the individual entities. In the course of evaluating the performance-enhancing effects of a wheat hydrolysate (HyPep 4601) in SP2/0 hybridoma cells cultivated in a CDM, an interesting result was observed when recombinant human serum albumin (rHSA) was included as an additional supplement.7

Figure 5
The data shown in Figure 5 show that supplementation with a combination of the wheat hydrolysate and rHSA yielded a significantly higher IgG titer than any other treatment. Although IgG titer increased by more than 30% in the cultures supplemented with rHSA alone, the IgG titer in the cultures supplemented with both HyPep 4601 and rHSA increased to greater than 180% of that of the medium control, despite the wheat hydrolysate's ineffectiveness as a solo supplement. This shows that cell culture supplements can act synergistically, dramatically improving the performance of a cell culture system when used in combination.

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