Insights into the Impact of Rosmarinic Acid on CHO Cell Culture Improvement through Transcriptomics Analysis

Abstract

The use of antioxidants in Chinese hamster ovary (CHO) cell cultures to improve monoclonal antibody production has been a topic of great interest. Nevertheless, the antioxidants do not have consistent benefits of production improvement, which might be cell line specific and/or process specific. In this work, we investigated how treatment with the antioxidant rosmarinic acid (RA) improved cell growth and titer in CHO cell cultures using transcriptomics. In particular, transcriptomics analysis indicated that RA treatment modified gene expression and strongly affected the MAPK and PI3K/Akt signaling pathways, which regulate cell survival and cell death. Moreover, it was observed that these signaling pathways, which had been identified to be up-regulated on day 2 and day 6 by RA, were also up-regulated over time (from initial growth phase day 2 to slow growth or protein production phase day 6) in both conditions. In summary, this transcriptomics analysis provides insights into the role of the antioxidant RA in industrial cell culture processes. The current study also represents an example in the industry of how omics can be applied to gain an in-depth understanding of CHO cell biology and to identify critical pathways that can contribute to cell culture process improvement and cell line engineering.