Significances of pH and temperature on the production of heat-shock protein glycoprotein 96 by MethA tumor cell suspension culture in stirred-tank bioreactors.
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.
Tang
Ya-Jie
YJ
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. yajietang@hotmail.com
Li
Hong-Mei
HM
Hamel
Jean-François P
JF
D000818:Animals; D019149:Bioreactors; D045744:Cell Line, Tumor; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013696:Temperature
D006023:Glycoproteins; D006360:Heat-Shock Proteins; D005973:Glutamine; D005947:Glucose