Quantifying the Impact of Media Supplementation on Cell Growth and Product Yield in Chinese Hamster Ovary (CHO) Cells
The optimization of cell growth and productivity is a major concern in the production of recombinant proteins in Chinese hamster ovary (CHO) cell cultures. Despite the frequency of media optimization in literature, there have been few attempts to comprehensively assess the overall effectiveness of media additives. This thesis aims to document media optimization (of CHO cell cultures) over the last 20 years and quantitatively assess the impact of media optimization on cell culture performance. A review of 78 studies identified 238 unique additive components, of which, trace elements stood out as having a positive impact on cell density while nucleosides show potential for increasing titer, with commercial supplements benefiting both. However, the impact of specific additives was found to be more variable than commonly perceived. With relatively few media studies considering multiple cell lines or multiple basal media, determining consistent and general trends becomes a considerable challenge. By extracting cell density and titer values from all of the reviewed studies, I was able to build a mixed-effect model capable of estimating the relative impact of additives, cell line, product type, basal medium, cultivation method (flask or reactor), and feeding strategy (batch or fed-batch). Overall, additives only accounted for 3% of the variation in cell density and 1% of the variation in titer. Similarly, the impact of basal media was also relatively modest, at 10% for cell density and 0% for titer. Cell line (10% and 13%), product type (9% and 33%), and feeding strategy (22% and 24%) were all found to have more impact on cell density and titer. These results emphasize the need for media studies to consider more factors to ensure that reported observations can be generalized and further developed.