Investigation of metabolic variability observed in extended fed batch cell culture

Biotechnology Progress

Volumn 29, Issue 6, 2013, Pages 1519-1527

  Gilbert, Alan ^a   Mcelearney, Kyle ^a   Kshirsagar, Rashmi ^a   Sinacore, Martin S ^a   Ryll, Thomas ^a  

^a BIOGEN   (United States)

Author keywords

Bioreactor; Cell culture; Metabolism; Mitochondrial membrane potential

Indexed keywords

FLUORESCENT STAINING; METABOLIC VARIABILITY; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL PATHWAYS; OPERATING CONDITION; PLATFORM PROCESS; PRODUCTION PROCESS; PRODUCTION RATES;

BATCH CELL CULTURE; BIOREACTORS; CELL CULTURE; MAGNESIUM PRINTING PLATES; MITOCHONDRIA;

METABOLISM;

GLUCOSE; IMMUNOGLOBULIN G; LACTIC ACID;

ANIMAL; ARTICLE; BATCH CELL CULTURE; BIOREACTOR; BIOSYNTHESIS; CELL CULTURE; CELL LINEAGE; CHO CELL LINE; CRICETULUS; CULTURE TECHNIQUE; METABOLISM; METHODOLOGY; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; OXYGEN CONSUMPTION;

BIOREACTOR; CELL CULTURE; METABOLISM; MITOCHONDRIAL MEMBRANE POTENTIAL;

ANIMALS; BATCH CELL CULTURE TECHNIQUES; BIOREACTORS; CELL CULTURE TECHNIQUES; CELL LINEAGE; CHO CELLS; CRICETULUS; GLUCOSE; IMMUNOGLOBULIN G; LACTIC ACID; MITOCHONDRIA; OXYGEN CONSUMPTION;

EID: 84890211017     PISSN: 87567938     EISSN: 15206033     Source Type: Journal    
DOI: 10.1002/btpr.1787     Document Type: Article

References (39)

1. Huang Y-M, Hu W, Rustandi E, Chang K, Yusuf-Makagiansar H, Ryll T. Maximizing productivity of CHO cell-based fed-batch culture using chemically defined media conditions and typical manufacturing equipment. Biotechnol Prog. 2010;26:1400-1410.
2. Lindgren K, Salmen A, Lundgren M, Bylund L, Ebler A, Faldt E, Sorvik L, Fenge C, Skoging-Nyberg U. Automation of cell line development. Cytotechnology. 2009;59:1-10.
3. Cacciatore JJ, Chasin LA, Leonard EF. Gene amplification and vector engineering to achieve rapid and high-level therapeutic protein production using the Dhfr-based CHO cell selection system. Biotechnol Adv. 2010;28:673-681.
4. Majors BS, Betenbaugh MJ, Pederson NE, Chiang GG. Enhancement of transient gene expression and culture viability using Chinese hamster ovary cells overexpressing Bcl-xL. Biotechnol Bioeng. 2008;101:567-578.
5. Cockett M, Bebbington C, Yarranton G. High level expression of tissue inhibitor of metalloproteinases in Chinese hamster ovary cells using glutamine synthetase gene amplification. Nat Biotechnol. 1990;8:662-667.
6. Nyberg GB, Balcarcel RR, Follstad BD, Stephanopoulos G, Wang DIC. Metabolism of peptide amino acids by Chinese hamster ovary cells grown in a complex medium. Biotechnol Bioeng. 2000;62:324-335.
7. Heidemann R, Zhang C, Qi H, Larrick Rule J, Rozales C, Park S, Chuppa S, Ray M, Michaels J, Konstantinov K. The use of peptones as medium additives for the production of a recombinant therapeutic protein in high density perfusion cultures of mammalian cells. Cytotechnology. 2000;32:157-167.
8. Franěk F, Hohenwarter O, Katinger H. Plant protein hydrolysates: preparation of defined peptide fractions promoting growth and production in animal cells cultures. Biotechnol Prog. 2008;16:688-692.
9. Urlaub G, Chasin LA. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci USA 1980;77:4216-4220.
10. Luo Y, Chen G. Combined approach of NMR and chemometrics for screening peptones used in the cell culture medium for the production of a recombinant therapeutic protein. Biotechnol Bioeng. 2007;97:1654-1659.
11. Sinacore MS, Drapeau D, Adamson S. Adaptation of mammalian cells to growth in serum-free media. Mol Biotechnol. 2000;15:249-257.
12. Van der Valk J, Brunner D, De Smet K, Fex Svenningsen Å, Honegger P, Knudsen LE, Lindl T, Noraberg J, Price A, Scarino ML. Optimization of chemically defined cell culture media-replacing fetal bovine serum in mammalian in vitro methods. Toxicol In Vitro. 2010;24:1053-1063.
13. Price PJ, Gregory EA. Relationship between in vitro growth promotion and biophysical and biochemical properties of the serum supplement. In Vitro Cell Develop Biol Plant. 1982;18:576-584.
14. Ma N, Ellet J, Okediadi C, Hermes P, McCormick E, Casnocha S. A single nutrient feed supports both chemically defined NS0 and CHO fed-batch processes: improved productivity and lactate metabolism. Biotechnol Prog. 2009;25:1353-1363.
15. Yu M, Hu Z, Pacis E, Vijayasankaran N, Shen A, Li F. Understanding the intracellular effect of enhanced nutrient feeding toward high titer antibody production process. Biotechnol Bioeng. 2011;108:1078-1088.
16. Li J, Gu W, Edmondson DG, Lu C, Vijayasankaran N, Figueroa B, Stevenson D, Ryll T, Li F. Generation of a cholesterol-independent, non-GS NS0 cell line through chemical treatment and application for high titer antibody production. Biotechnol Bioeng. 2012;109:1685-1692.
17. Fong MY, McDunn J, Kakar SS. Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer. PLoS ONE. 2011;6:e19963.
18. Dietmair S, Timmins NE, Gray PP, Nielsen LK, Krömer JO. Towards quantitative metabolomics of mammalian cells: development of a metabolite extraction protocol. Anal Biochem. 2010;404:155-164.
19. Schaub J, Clemens C, Kaufmann H, Schulz T. Advancing biopharmaceutical process development by system-level data analysis and integration of omics data. In: Hu WS, Zeng A, editors. Genomics and Systems Biology of Mammalian Cell Culture. Berlin Heidelberg: Springer; 2012:133-163.
20. Sengupta N, Rose ST, Morgan JA. Metabolic flux analysis of CHO cell metabolism in the late non-growth phase. Biotechnol Bioeng. 2011;108:82-92.
21. Ahn WS, Antoniewicz MR. Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metabol Eng. 2011;13:598-609.
22. Ahn WS, Antoniewicz MR. Towards dynamic metabolic flux analysis in CHO cell cultures. Biotechnol J. 2012;7:61-74.
23. 13C isotopic tracers for metabolic flux analysis in mammalian cells. J Biotechnol. 2009;144:167-174.
24. Goudar C, Biener R, Boisart C, Heidemann R, Piret J, de Graaf A, Konstantinov K. Metabolic flux analysis of CHO cells in perfusion culture by metabolite balancing and 2D [13 C, 1 H] COSY NMR spectroscopy. Metabol Eng. 2010;12:138.
25. Prentice HL, Ehrenfels BN, Sisk WP. Improving performance of mammalian cells in fed-batch processes through "bioreactor evolution". Biotechnol Prog. 2007;23:458-464.
26. Chiang GG, Sisk WP. Bcl-xL mediates increased production of humanized monoclonal antibodies in Chinese hamster ovary cells. Biotechnol Bioeng. 2005;91:779-792.
27. Kshirsagar R, McElearney K, Gilbert A, Sinacore M, Ryll T. Controlling trisulfide modification in recombinant monoclonal antibody produced in fed-batch cell culture. Biotechnol Bioeng. 2012;109:2523-2532.
28. Henderson JW, Ricker RD, 2006. Bidlingmeyer BA, Woodward C. Rapid, accurate, sensitive and reproducible analysis of amino Acids. Palo Alto, CA: Agilent Technologies 5980-1193EN.
29. Johnson LV, Walsh ML, Chen LB. Localization of mitochondria in living cells with rhodamine 123. Proc Natl Acad Sci USA. 1980;77:990-994.
30. Johnson LV, Walsh ML, Bockus BJ, Chen LB. Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy. J Cell Biol. 1981;88:526-535.
31. Goudar CT, Piret JM, Konstantinov KB. Estimating cell specific oxygen uptake and carbon dioxide production rates for mammalian cells in perfusion culture. Biotechnol Prog. 2011;27:1347-1357.
32. Schneider M, Marison IW, von Stockar U. The importance of ammonia in mammalian cell culture. J Biotechnol. 1996;46:161-185.
33. Martinelle K, Häggström L. Mechanisms of ammonia and ammonium ion toxicity in animal cells: transport across cell membranes. J Biotechnol. 1993;30:339-350.
34. John AP. Dysfunctional mitochondria, not oxygen insufficiency, cause cancer cells to produce inordinate amounts of lactic acid: the impact of this on the treatment of cancer. Med Hypotheses. 2001;57:429-431.
35. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M, Wehrli S, Thompson CB. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA. 2007;104:19345-19350.
36. Vazquez A, Liu J, Zhou Y, Oltvai ZN. Catabolic efficiency of aerobic glycolysis: the Warburg effect revisited. Bmc Syst Biol. 2010;4:58.
37. Sauerwald TM, Figueroa B, Hardwick JM, Oyler GA, Betenbaugh MJ. Combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit cell death in mammalian cell cultures. Biotechnol Bioeng. 2006;94:362-372.
38. Cheng EHYA, Wei MC, Weiler S, Flavell RA, Mak TW, Lindsten T, Korsmeyer SJ. BCL-2, BCL-XL sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol Cell. 2001;8:705-711.
39. Shimizu S, Eguchi Y, Kamiike W, Funahashi Y, Mignon A, Lacronique V, Matsuda H, Tsujimoto Y. Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating protonflux. Proc Natl Acad Sci USA. 1998;95:1455-1459.