Adaptation of Chinese hamster ovary cells to high potassium ion-containing medium for enhancement of follicle-stimulating hormone production

Abstract

In this study, a suspension culture of recombinant Chinese hamster ovary (CHO) cells producing follicle-stimulating hormone (FSH) was used to investigate the effects of potassium ion (K⁺) on cell growth and FSH production. Cell growth was significantly suppressed at a K⁺ concentration higher than 60 mM, but specific FSH productivity (q _FSH) was enhanced more than 2-fold compared to the value obtained at 4 mM K⁺. In an attempt to alleviate the cell growth suppression at a high K⁺ concentration, the cells were adapted at 60 mM K⁺ in a repeated batch mode. During adaptation, the growth rate increased from 0.010 to 0.020 h⁻¹, andq _FSH also gradually increased and reached 11.1 ng/(10⁶ cells h), which was even higher than that of the unadapted cells at 60 mM K⁺. The adapted cells showed a 2.6-fold increase in maximum FSH titer at 80 mM K⁺ compared to the unadapted cells at 4 mM K⁺. Taken together, these results demonstrate the potential of using culture media containing cells adapted to high K⁺ concentrations, for the enhancement of recombinant protein production.