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Population‐based modeling of the progression of apoptosis in mammalian cell culture
Author(s) -
Meshram Mukesh,
Naderi Saeideh,
McConkey Brendan,
Budman Hector,
Scharer Jeno,
Ingalls Brian
Publication year - 2012
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.24392
Subject(s) - apoptosis , chinese hamster ovary cell , cell culture , programmed cell death , monoclonal antibody , microbiology and biotechnology , biology , intracellular , population , cell growth , cell , antibody , biochemistry , immunology , genetics , medicine , environmental health
The production of biopharmaceuticals from mammalian cell culture is hindered by apoptosis, which is the primary cause of cell death in these cultures. As a tool for optimization of culture yield, this study presents a population‐based model describing the progression of apoptosis in a monoclonal antibody (mAb)‐producing Chinese hamster ovary (CHO) cell culture. Because mAb production does not cease when apoptosis begins, the model was designed to incorporate subpopulations at various stages in the progression of apoptosis. The model was validated against intracellular measurements of caspase activity as well as cell density, nutrient levels, and toxic metabolites. Since the specific details of apoptotic mechanisms have not been elucidated in this cell line, we employed a model comparison analysis that suggests the most plausible pathways of activation. Biotechnol. Bioeng. 2012; 109:1193–1204. © 2011 Wiley Periodicals, Inc.