Impact of sodium butyrate and mild hypothermia on metabolic and physiological behaviour of CHO TF 70R cells

Veronica Avello, Bethzabeth Tapia, Mauricio Vergara, Cristian Acevedo, Julio Berrios, Juan G. Reyes, Claudia Altamirano

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background To reduce costs associated with productivity of recombinant proteins in the biopharmaceutical industry, research has been focused on regulatory principals of growth and survival during the production phases of the cell culture. The main strategies involve the regulation of cell proliferation by the modulation of cell cycle control points (G1/S or G2/M) with mild hypothermia and the addition of sodium butyrate (NaBu). In this study, batch culture strategies were evaluated using CHO TF 70R cells producing the recombinant human tissue plasminogen activator (rh-tPA), to observe their individual and combined effect on the cellular physiological state and relevant kinetic parameters. Results NaBu addition has a negative effect on the mitochondrial membrane potential (∆ Ψm), the values of which are remarkably diminished in cultures exposed to this cytotoxic compound. This effect was not reflected in a loss of cell viability. NaBu and mild hypothermic conditions increased the doubling time in the cell cultures, suggesting that these strategies triggered a general slowing of each cell cycle phase in a different way. Finally, the individual and combined effect of NaBu and mild hypothermia produced an increase in the specific rh-tPA productivity in comparison to the control at 37°C without NaBu. Nevertheless, both strategies did not have a synergistic effect on the specific productivity. Conclusions The combination of NaBu addition and mild hypothermic condition causes an impact on physiological and metabolic state of CHO TF 70R cells, decreasing cell growth rate and improving glucose consumption efficiency. These results therefore provide a promising strategy to increase specific productivity of rh-tPA.

Original languageEnglish
Pages (from-to)55-62
Number of pages8
JournalElectronic Journal of Biotechnology
Volume27
DOIs
StatePublished - May 2017
Externally publishedYes

Keywords

  • Cell cycle modulation
  • Cell viability
  • Chinese hamster ovary
  • Combined effect
  • Cytotoxic
  • Mitochondrial membrane potential
  • Recombinant human tissue plasminogen activator
  • Recombinant proteins
  • Regulation of cell proliferation
  • Sodium butyrate
  • rh-tPA production

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