Significances of pH and temperature on the production of heat-shock protein glycoprotein 96 by MethA tumor cell suspension culture in stirred-tank bioreactors

Abstract

Heat-shock protein, glycoprotein 96 (gp96), elicits both innate and adaptive immune responses against tumors or viral infections. In our laboratory, MethA tumor cell suspension culture process has been recently developed for gp96 production in spinner flask. In this work, significances of pH and temperature on the novel bioprocess were studied in stirred-tank bioreactor. Lowering of culture pH and temperature led to a significant reduction of average specific growth rate but cell viability remained high for a prolonged cultivation time resulting in a higher integral of viable cells. Both the maximal viable cell density and gp96 production were attained at a pH of 7.0. Interestingly, gp96 production was increased above and below 37 degrees C, presumably because gp96 biosynthesis was induced when MethA tumor cell underwent heat or cold. For MethA tumor cell growth 37 degrees C was desirable, while gp96 production and productivity was obtained at their peak values at 40 degrees C. The results of this work might be useful to scale-up the bioprocess into the pilot scale.

Transcriptomic and Metabolomic Analyses Provide Insights into the Growth and Development Advantages of Triploid Apostichopus japonicus

“…The up-regulated expression of HSC70 gene can protect against injury due to high temperature (Sun et al 2016 ). GP96 is highly expressed following increased temperature; therefore, it can resist high temperature (Tang et al 2009 ). This may be the reason why the aestivation time of triploid A. japonicus is shorter.…”

Colorimetric pH measurement of animal cell culture media

“…Use of pH monitoring during a bioprocess is vital because the pH of an animal cell culture medium directly affects the cellular growth, proliferation, and target protein productivity (Tang et al 2009). Even extracellular pH changes for a few minutes can considerably influence the synthesis of cellular matrix components (Wu et al 2007).…”