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Effects of elevated pCO 2 and/or osmolality on the growth and recombinant tPA production of CHO cells
Author(s) -
Kimura Roy,
Miller William M.
Publication year - 1996
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/(sici)1097-0290(19961005)52:1<152::aid-bit15>3.0.co;2-q
Subject(s) - pco2 , osmole , bicarbonate , chemistry , chinese hamster ovary cell , osmotic concentration , carbon dioxide , sodium bicarbonate , hydrolysate , hamster , medicine , endocrinology , biochemistry , biology , receptor , hydrolysis , organic chemistry
Carbon dioxide is a by‐product of mammalian cell metabolism that will build up in culture if it is not removed from the medium. Increased carbon dioxide levels are generally not a problem in bench‐top bioreactors, but inhibitory levels can easily be reached in large‐scale vessels, especially if the aeration gas is enriched in oxygen. Due to the equilibrium attained between dissolved CO 2 and bicarbonate, increased pCO 2 is associated with increased osmolality in bioreactors with pH control. While a few preliminary reports indicate that elevated pCO 2 levels can inhibit cell growth and/or recombinant protein production, no comprehensive analysis of the interrelated effects of elevated pCO 2 and osmolality has been published. We have examined the effects of 140, 195, and 250 mm Hg (187, 260, and 333 mbar, respectively) pCO 2 (with and without osmolality control) on the growth of and recombinant tPA production by MT2‐1‐8 Chinese hamster ovary (CHO) cells. The effects of elevated osmolality were also investigated at the control pCO 2 of 36 mm Hg. Elevated pCO 2 at 310 mOsm/kg osmolality inhibited cell growth in a dose‐dependent fashion, with a maximum decrease of 30% in the specific growth rate (μ) at 250 mm Hg. Osmolality alone had no effect on μ, but the combination of elevated pCO 2 and osmolality increased the maximal reduction in μ to 45%. Elevated pCO 2 at 310 mOsm/kg osmolality decreased the specific tPA production rate ( q tPA ) by up to 40% at 250 mm Hg. Interestingly, while increased osmolality decreased q tPA significantly at 140 mm Hg pCO 2 , it had no effect or even increased q tPA at 195 and 250 mm Hg. © 1996 John Wiley & Sons, Inc.