Differential effect of culture temperature and specific growth rate on CHO cell behavior in chemostat culture.
Mild hypothermia condition in mammalian cell culture technology has been one of the main focuses of research for the development of breeding strategies to maximize productivity of these production systems. Despite the large number of studies that show positive effects of mild hypothermia on specific productivity of r-proteins, no experimental approach has addressed the indirect effect of lower temperatures on specific cell growth rate, nor how this condition possibly affects less specific productivity of r-proteins. To separately analyze the effects of mild hypothermia and specific growth rate on CHO cell metabolism and recombinant human tissue plasminogen activator productivity as a model system, high dilution rate (0.017 h(-1)) and low dilution rate (0.012 h(-1)) at two cultivation temperatures (37 and 33 °C) were evaluated using chemostat culture. The results showed a positive effect on the specific productivity of r-protein with decreasing specific growth rate at 33 °C. Differential effect was achieved by mild hypothermia on the specific productivity of r-protein, contrary to the evidence reported in batch culture. Interestingly, reduction of metabolism could not be associated with a decrease in culture temperature, but rather with a decrease in specific growth rate.
School of Biochemical Engineering, Pontificia Universidad Católica de Valparaiíso, Valparaíso, Chile.
Mauricio
M
Vergara
School of Biochemical Engineering, Pontificia Universidad Católica de Valparaiíso, Valparaíso, Chile; CREAS CONICYT-REGIONAL, GORE Valparaíso, Valparaíso, Chile.
Silvana
S
Becerra
School of Biochemical Engineering, Pontificia Universidad Católica de Valparaiíso, Valparaíso, Chile.
Julio
J
Berrios
Institute of Chemistry, Pontificia Universidad Católica de Valparaiíso, Valparaíso, Chile.
Nelson
N
Osses
Institute of Chemistry, Pontificia Universidad Católica de Valparaiíso, Valparaíso, Chile.
Juan
J
Reyes
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, United States of America.
María
M
Rodríguez-Moyá
Department of Chemical and Biomolecular Engineering, Rice University, Houston, Texas, United States of America; Department of Bioengineering, Rice University, Houston, Texas, United States of America.
Ramon
R
Gonzalez
School of Biochemical Engineering, Pontificia Universidad Católica de Valparaiíso, Valparaíso, Chile; CREAS CONICYT-REGIONAL, GORE Valparaíso, Valparaíso, Chile.
Claudia
C
Altamirano
D000818:Animals; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D003080:Cold Temperature; D003412:Cricetulus