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Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition
Author(s) -
Wolf Moritz K. F,
Closet Aurélie,
Bzowska Monika,
Bielser JeanMarc,
Souquet Jonathan,
Broly Hervé,
Morbidelli Massimo
Publication year - 2019
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201700722
Subject(s) - cell growth , product inhibition , cell culture , microbiology and biotechnology , yield (engineering) , perfusion , cell , bleed , chemistry , biophysics , biology , biochemistry , materials science , medicine , non competitive inhibition , metallurgy , genetics , enzyme , art , visual arts
Mammalian cell perfusion cultures represent a promising alternative to the current fed‐batch technology for the production of various biopharmaceuticals. Long‐term operation at a fixed viable cell density (VCD) requires a viable culture and a constant removal of excessive cells. Product loss in the cell removing bleed stream deteriorates the process yield. In this study, the authors investigate the use of chemical and environmental growth inhibition on culture performance by either adding valeric acid (VA) to the production media or by reducing the culture temperature (33.0 °C) with respect to control conditions (36.5 °C, no VA). Low temperature significantly reduces cellular growth, thus, resulting in lower bleed rates accompanied by a reduced product loss of 11% compared to 26% under control conditions. Additionally, the cell specific productivity of the target protein improves and maintained stable leading to media savings per mass of product. VA shows initially an inhibitory effect on cellular growth. However, cells seemed to adapt to the presence of the inhibitor resulting in a recovery of the cellular growth. Cell cycle and Western blot analyses support the observed results. This work underlines the role of temperature as a key operating variable for the optimization of perfusion cultures.