3 years ago

Intracellular Response of CHO Cells to Oxidative Stress and its Influence on Metabolism and Antibody Production

Intracellular Response of CHO Cells to Oxidative Stress and its Influence on Metabolism and Antibody Production
Chinese hamster ovary (CHO) cells are widely used for the manufacture of therapeutic mAbs with high productivity processes generating 5–10 g/L mAb. High productivity processes impose considerable strain on the intracellular metabolic and redox homeostasis resulting in increased oxidative stress. We investigated the mechanisms by which oxidative stress affects the productivity of a mAb producing CHO cell line by controlling bioreactors at dissolved oxygen (DO) set-points ranging from 20-175% of air saturation. The results showed that for the 20-75% DO conditions, despite similar growth and viability, there were significant differences in productivity, consumptions of oxygen and amino acids, intracellular redox, and mitochondrial function. Our results demonstrate that as the external dissolved oxygen increased, intracellular H2O2 increased, mitochondrial function diminished, flux into one-carbon metabolism pathway decreased, and cells diverted metabolic activity from mAb production. Intriguingly, although the reductase activities were similar irrespective of the DO concentration, the intracellular reduced-to-oxidized glutathione ratios were low for all conditions, which demonstrated that the intracellular antioxidant mechanisms had difficulties managing oxidative stress. Combined, these results indicate that mAb production may be limited by the cell’s capacity to manage oxidative stress and thus provide a new attribute to leverage during upstream process development.

Publisher URL: www.sciencedirect.com/science

DOI: S1369703X18300408

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.