A New Era in Cell Culture Media Development - Cell-line specific complex media supplements combine complex or chemically defined, animal-component free media additives into a single homogeneous functi

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A New Era in Cell Culture Media Development
Cell-line specific complex media supplements combine complex or chemically defined, animal-component free media additives into a single homogeneous functional supplement.


BioPharm International
Volume 25, Issue 7, pp. 28-35

HYDROLYSATES AS SERUM REPLACEMENTS

Plant-based hydrolysates were one of the first nonanimal-derived supplements to replace serum and performed as a robust media across a variety of cell lines and types. Known to provide amino acids, peptides, carbohydrates, vitamins, and minerals, hydrolysate supplements have delivered growth rates and product titers comparable to serum or complex chemically defined media.

A recent study examined hydrolysate fractions to determine functionality. Interestingly, not only were hydrolysates found to be an important source of free amino acids but also appeared to stimulate more efficient cell metabolism. In addition, the oligonucleotide fraction was found to remain largely intact during culture conditions, suggesting a role other than as nutrition, such as a possible protective role from shear stress or anti-apoptotic function to promote enhanced growth and productivity.

This effect on cell metabolism has been observed for both hybridoma (Sp2/0) and Chinese hamster ovary cells (CHO) cultured in chemically defined media (CDM) supplemented with plant-based hydrolysates. A metabolic shift was observed where the cultured cells began to metabolize lactate as the carbon source once glucose and glutamine had almost been consumed. In addition, both glucose and glutamine were consumed at a more rapid rate in supplemented cultures.


Figure 1: A metabolic shift occurred when Chinese hamster ovary (CHO) cells were cultured in chemically defined media plus plant-based hydrolysate (HyPep 1510), resulting in increased cell density and productivity. (ALL FIGURES ARE COURTESY OF THE AUTHOR)
Accumulation of lactate during mammalian cell culture is a major concern because it can adversely affect cell growth and product quality. The metabolic shift observed when CDM was supplemented with plant-based hydrolysates resulted in an extended growth period and significant increase in product titer (see Figure 1).

NEW PLATFORM TO ADDRESS HYDROLYSATE DEFINITION AND VARIATION

Plant-derived protein hydrolysates have been shown to be an effective replacement for serum and animal-derived components, delivering consistent benefits to cell performance parameters. Although the manufacture of these products is well controlled, hydrolysates by their own nature are complex and not fully defined.

With the aim of streamlining biologic production processes and reducing costs, consistency and predictability are becoming a major focus for the biotech industries. Acknowledging these trends, a new hydrolysate platform has been developed, which maintains the animal-free requirements of the supplement while minimizing variability issues and delivering a more reproducible product.

The production process is based on an innovative approach to enzymatic digestion involving a non-animal enzyme cocktail of both proteases and nonproteolytic enzymes. The highly optimized process is designed to expand the range of nutritional factors available to the cell, providing growth-promoting peptides as well as essential amino acids, carbohydrates, lipids, minerals, and vitamins. Importantly, product consistency can be enhanced and interlot variability can be reduced because the process requires fewer process steps.


Figure 2: Chinese hamster ovary (CHO) cell cultures supplemented with yeast hydrolysate maintained higher cell densities compared with chemically defined medium (a) translating to an increase in product titer (b); YE is yeast extract; UFYE is ultrafiltered yeast hydrolysate.
Experimental data obtained from the comparison of CHO cells cultured in CDM alone to CDM supplemented with ultrafiltered yeast extract (UFYE) demonstrated significant performance benefits in the supplemented cultures. Peak cell density was achieved earlier in culture and was maintained for longer for UFYE when compared with the CDM control (see Figure 2a). The effect on cell growth translated to a significant increase in product titer (see Figure 2b).


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