Quantifying the impact of cell culture media on CHO cell growth and protein production. Combe Michelle,Sokolenko Stanislav Biotechnology advances In recombinant protein production, cell culture media development and optimization is typically seen as a useful strategy to increase titer and cell density, reduce by-products, as well as improve product quality (with cell density and titer often serving as the primary reported outcome of media studies). However, despite the large number of media optimization studies, there have been few attempts to comprehensively assess the overall effectiveness of media additives. The aim of this review is therefore both to document published media optimization studies over the last twenty years (in the context of Chinese hamster ovary cell recombinant production) and quantitatively estimate the impact of this media optimization on cell culture performance. In considering 78 studies, we have identified 238 unique media components that have been supplemented over the last 20 years. Among these additives, trace elements stood out as having a positive impact on cell density while nucleotides show potential for increasing titer, with commercial supplements benefiting both. However, we also identified that the impact of specific additives is far more variable than often perceived. With relatively few media studies considering multiple cell lines or multiple basal media, teasing out consistent and general trends becomes a considerable challenge. By extracting cell density and titer values from all of the reviewed studies, we were 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, product type, and feeding strategy were all found to have more impact. These results emphasize the need for media studies to consider more factors to ensure that reported observations can be generalized and further developed. 10.1016/j.biotechadv.2021.107761

A review of algorithmic approaches for cell culture media optimization. Frontiers in bioengineering and biotechnology Cell culture media composition and culture conditions play a crucial role in product yield, quality and cost of production. Culture media optimization is the technique of improving media composition and culture conditions to achieve desired product outcomes. To achieve this, there have been many algorithmic methods proposed and used for culture media optimization in the literature. To help readers evaluate and decide on a method that best suits their specific application, we carried out a systematic review of the different methods from an algorithmic perspective that classifies, explains and compares the available methods. We also examine the trends and new developments in the area. This review provides recommendations to researchers regarding the suitable media optimization algorithm for their applications and we hope to also promote the development of new cell culture media optimization methods that are better suited to existing and upcoming challenges in this biotechnology field, which will be essential for more efficient production of various cell culture products. 10.3389/fbioe.2023.1195294