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.
James Babcock, PhD, is the global applications manager of cell culture at the Sheffield Bio-Science Center for Cell Culture Technology.
Articles by James Babcock, PhD
Christopher Wilcox, PhD, is the global market segment manager of cell culture at Sheffield Bio-Science, a Kerry Group Business
Articles by Christopher Wilcox, PhD
Hans Huttinga
Hans Huttinga is the global business development director of cell nutrition at Sheffield Bio-Science, a Kerry Group Business
Articles by Hans Huttinga
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