"What We Do in Life Echoes in Eternity"

… And similarly, how you treat your cells during isolation and expansion impacts your final yield (apologies to Russell Crowe, both for the quote and the image below 😂).

Animal cells, crucial in biomanufacturing, are highly responsive to their environment. To produce commercial quantities of downstream products, it’s vital to optimize every part of the process. This includes selecting the top-performing cell line, using the most suitable media, and refining the process for maximum efficiency. But, is scaling up the upstream bioprocess simply a matter of repeating the same steps on a larger scale? Recent research suggests otherwise. 📈

A notable study by Moran et al. (linked here) explored the impact of different expansion strategies on CHO cells. Cells expanded using a fed-batch process and allowed to reach the plateau phase showed higher yields in the final manufacturing stage—both in terms of cell numbers and titer—compared to cells expanded through traditional media replacements every few days while maintaining logarithmic growth. Interestingly, despite slower growth rates in the fed-batch approach, the peak yields were superior. 📊

This ties back to the intricate relationship between cell metabolism and epigenetic markers, indicating that changes in the upstream process can significantly influence downstream outcomes. This study highlights how every step, from initial cell isolation to the N-1 stage, plays a crucial role in determining final yields. 🔬

One of the best examples of an upstream intervention impacting downstream process is an old paper from Mark Post demonstrating that muscle stem cells cultured in the presence of a p38/MAPK inhibitor exhibited an increased rate of proliferation, but when the inhibitor was removed and the cells were induced to differentiate, they also showed an increased capacity for myotube formation (linked here).