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Mitochondrial Membrane Potential Selects Hybridomas Yielding High Viability in Fed‐Batch Cultures
Author(s) -
Follstad Brian D.,
Wang Daniel I. C.,
Stephanopoulos Gregory
Publication year - 2002
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp010132b
Subject(s) - rhodamine 123 , apoptosis , biology , population , microbiology and biotechnology , membrane potential , viability assay , mitochondrion , cell , cell culture , inner mitochondrial membrane , biochemistry , genetics , demography , sociology , multiple drug resistance , antibiotics
Prior research (Follstad, B. D.; Wang, D. I. C.; Stephanopoulos, G. Mitochondrial membrane potential differentiates cells resistant to apoptosis in hybridoma cultures. Eur. J. Biochem . 2000 , 267 , 6534–6540.) identified mitochondrial membrane potential (MMP) as a marker of hybridoma subpopulations resistant to apoptosis caused by a variety of apoptosis inducers. In this study, we investigated the viability of hybridoma cell cultures inoculated with cells of varying MMP in regular fed‐batch operation. A hybridoma cell population was separated using FACS into subpopulations based on their mean mitochondrial membrane potential (MMP) as measured using the common mitochondrial stain, Rhodamine 123 (Rh123). These subpopulations showed dramatic differences in their apoptotic death kinetics. Fed‐batches inoculated with a high MMP subpopulation reached higher viable cell concentrations and viabilities that were maintained for prolonged periods of time relative to fed‐batches inoculated with low MMP subpopulations. These results underline the heterogeneous nature of hybridoma cell cultures and suggest that mitochondrial physiology is a critical parameter determining culture performance.