Decoupling cell growth and product formation in Chinese hamster ovary cells through metabolic control

CLAUDIA VICTORIA ALTAMIRANO GOMEZ, J. J. Cairó, F. Gòdia

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The development of a strategy for the culture of Chinese hamster ovary (CHO) cells producing tissue plasminogen activator (t-PA) is investigated. This strategy is based on the replacement of the main carbon source, glucose, by another compound that is slowly metabolizable, particularly galactose. The introduction of this change allows for acute change in cell behavior at various levels. Cell growth is stopped after this nutrient shift, and the cells can be kept in long-duration culture at a low growth rate and high viability as compared with a culture strategy based solely on glucose utilization. Moreover, the capability of cells to produce recombinant proteins (t-PA in this work) can be maintained over the entire period of galactose feeding. From the metabolic point of view, use of a slowly metabolizable carbon source (galactose) introduces important changes in the production of lactate, ammonia, and some amino acids. The use of this metabolic shift enables the generation of biphasic processes, with a first phase with cell growth on glucose and a second stationary phase on galactose, which is particularly suited to perfusion systems.

Original languageEnglish
Pages (from-to)351-360
Number of pages10
JournalBiotechnology and Bioengineering
Volume76
Issue number4
DOIs
StatePublished - 8 Nov 2001

Keywords

  • Arrested cells
  • Biphasic culture
  • Chinese hamster ovary (CHO) cells
  • Glutamate and glucose replacement

Fingerprint Dive into the research topics of 'Decoupling cell growth and product formation in Chinese hamster ovary cells through metabolic control'. Together they form a unique fingerprint.

Cite this