Effects of lactate concentration on hybridoma culture in lactate‐controlled fed‐batch operation

Abstract

To investigate the effects of lactate on cell growth and antibody production, a new method of maintaining the lactate concentration constant in a fed-batch culture is described. When the pH was initially adjusted by sodium hydroxide, the specific growth rate decreased and specific death rate increased with an increase of lactate concentration. To investigate whether the inhibition was due to the lactate concentration itself or to the osmotic pressure, the effect of the osmotic pressure adjusted by sodium chloride was compared with that of sodium lactate. When the osmotic pressure was adjusted to same condition as that of sodium lactate using sodium chloride, the specific growth data showed the same degree of growth inhibition. It was thus evident that the inhibition to cell growth was mainly due to osmotic pressure while lactate production from glucose was found to be inhibited by the lactate itself compared with sodium chloride. The specific antibody production rate had a maximum value within a certain range of lactate concentration. Moreover, specific antibody production rate had a unified relationship with the kinetic parameter mu, in spite of the different causes of inhibition by lithium lactate and sodium lactate. A certain "trade-off" relationship between growth and antibody production existed at higher growth rates.

CD147 silencing via RNA interference reduces tumor cell invasion, metastasis and increases chemosensitivity in pancreatic cancer cells

“…The results also showed that CD147 silencing resulted in an increase of the intracellular lactate concentration in pancreatic cancer cells. The increase of lactate concentration may inhibit the cell growth, since lactate has been demonstrated to decrease pyruvate reduction to lactate by inhibition of (LDH) (39). However, the present results did not show that the increase of lactate concentration inhibited the proliferation in Panc-1 cells (data not shown), and we will investigate the mechanism in the future.…”

Effect of Polyphenols on Reactive Oxygen Species Production and Cell Growth of Human Dermal Fibroblasts after Irradiation with Ultraviolet-A Light

“…The change in cell density is presented as the mean of two independent experiments. The specific growth rate was calculated from the total cell density and incubation time during 72 h-culture Omasa et al, 1992 .…”

Enhanced glycoprotein production in HEK-293 cells expressing pyruvate carboxylase

“…They are well known inhibitors of both cellular growth and productivity, with detrimental effects reported for lactate levels exceeding 20 mM and ammonia concentrations as low as 2-3 mM (Cruz et al, 2000;Glacken, 1986;Hassell et al, 1991;Omasa et al, 1992a;Ozturk et al, 1992). Moreover, these metabolites were shown to adversely affect product quality, most notablybyalteringtheglycosylationpattern (Andersen and Goochee, 1995;Borys et al, 1994;Chen and Harcum, 2006;Gawlitzek et al, 1998;Grammatikos et al, 1998).…”

“…At the process level, the apparent deregulation of glucose and glutamine uptake rates when these nutrients are present in excess has led to the implementation of controlled feeding strategies to maintain low but non-limiting levels of the main nutrient concentrations (Europa et al, 2000;Gambhir et al, 1999;Kurokawa et al, 1994;Lee et al, 2003;Haggstrom, 1992, 1994;Omasa et al, 1992aOmasa et al, , 1992bSiegwart et al, 1999;Zhou et al, 1995). Such strategies have proven effective at reducing the overall yield of lactate on glucose, but require on-line monitoring of nutrient concentrations and automatic feed rate adjustment during the culture.…”