Decoupling cell growth and product formation in Chinese hamster ovary cells through metabolic control
The development of a strategy for the culture of Chinese hamster ovary (CHO) cells producing tissue plasminogen activator (t‐PA) is investigated. This strategy is based on the replacement of the main carbon source, glucose, by another compound that is slowly metabolizable, particularly galactose. Th...
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| Veröffentlicht in: | Biotechnology and bioengineering 2001-12, Vol.76 (4), p.351-360 |
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| creator | Altamirano, C. Cairó, J. J. Gòdia, F. |
| description | The development of a strategy for the culture of Chinese hamster ovary (CHO) cells producing tissue plasminogen activator (t‐PA) is investigated. This strategy is based on the replacement of the main carbon source, glucose, by another compound that is slowly metabolizable, particularly galactose. The introduction of this change allows for acute change in cell behavior at various levels. Cell growth is stopped after this nutrient shift, and the cells can be kept in long‐duration culture at a low growth rate and high viability as compared with a culture strategy based solely on glucose utilization. Moreover, the capability of cells to produce recombinant proteins (t‐PA in this work) can be maintained over the entire period of galactose feeding. From the metabolic point of view, use of a slowly metabolizable carbon source (galactose) introduces important changes in the production of lactate, ammonia, and some amino acids. The use of this metabolic shift enables the generation of biphasic processes, with a first phase with cell growth on glucose and a second stationary phase on galactose, which is particularly suited to perfusion systems. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 351–360, 2001. |
| doi_str_mv | 10.1002/bit.10096 |
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J. ; Gòdia, F.</creator><creatorcontrib>Altamirano, C. ; Cairó, J. J. ; Gòdia, F.</creatorcontrib><description>The development of a strategy for the culture of Chinese hamster ovary (CHO) cells producing tissue plasminogen activator (t‐PA) is investigated. This strategy is based on the replacement of the main carbon source, glucose, by another compound that is slowly metabolizable, particularly galactose. The introduction of this change allows for acute change in cell behavior at various levels. Cell growth is stopped after this nutrient shift, and the cells can be kept in long‐duration culture at a low growth rate and high viability as compared with a culture strategy based solely on glucose utilization. Moreover, the capability of cells to produce recombinant proteins (t‐PA in this work) can be maintained over the entire period of galactose feeding. From the metabolic point of view, use of a slowly metabolizable carbon source (galactose) introduces important changes in the production of lactate, ammonia, and some amino acids. The use of this metabolic shift enables the generation of biphasic processes, with a first phase with cell growth on glucose and a second stationary phase on galactose, which is particularly suited to perfusion systems. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 351–360, 2001.</description><identifier>ISSN: 0006-3592</identifier><identifier>EISSN: 1097-0290</identifier><identifier>DOI: 10.1002/bit.10096</identifier><identifier>PMID: 11745163</identifier><identifier>CODEN: BIBIAU</identifier><language>eng</language><publisher>New York: John Wiley & Sons, Inc</publisher><subject>Amino Acids - chemistry ; Ammonia - chemistry ; Animal cells ; Animals ; arrested cells ; Biological and medical sciences ; Biotechnology ; biphasic culture ; Carbon - chemistry ; Cell Culture Techniques - methods ; Cell Division ; Cells, Cultured ; Chinese hamster ovary (CHO) cells ; CHO Cells ; Cricetinae ; Establishment of new cell lines, improvement of cultural methods, mass cultures ; Eukaryotic cell cultures ; Fundamental and applied biological sciences. Psychology ; galactose ; Galactose - chemistry ; glucose ; Glucose - chemistry ; Glucose - metabolism ; glutamate and glucose replacement ; Lactic Acid - chemistry ; Methods. Procedures. 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J.</creatorcontrib><creatorcontrib>Gòdia, F.</creatorcontrib><title>Decoupling cell growth and product formation in Chinese hamster ovary cells through metabolic control</title><title>Biotechnology and bioengineering</title><addtitle>Biotechnol. Bioeng</addtitle><description>The development of a strategy for the culture of Chinese hamster ovary (CHO) cells producing tissue plasminogen activator (t‐PA) is investigated. This strategy is based on the replacement of the main carbon source, glucose, by another compound that is slowly metabolizable, particularly galactose. The introduction of this change allows for acute change in cell behavior at various levels. Cell growth is stopped after this nutrient shift, and the cells can be kept in long‐duration culture at a low growth rate and high viability as compared with a culture strategy based solely on glucose utilization. Moreover, the capability of cells to produce recombinant proteins (t‐PA in this work) can be maintained over the entire period of galactose feeding. From the metabolic point of view, use of a slowly metabolizable carbon source (galactose) introduces important changes in the production of lactate, ammonia, and some amino acids. The use of this metabolic shift enables the generation of biphasic processes, with a first phase with cell growth on glucose and a second stationary phase on galactose, which is particularly suited to perfusion systems. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 351–360, 2001.</description><subject>Amino Acids - chemistry</subject><subject>Ammonia - chemistry</subject><subject>Animal cells</subject><subject>Animals</subject><subject>arrested cells</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>biphasic culture</subject><subject>Carbon - chemistry</subject><subject>Cell Culture Techniques - methods</subject><subject>Cell Division</subject><subject>Cells, Cultured</subject><subject>Chinese hamster ovary (CHO) cells</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Establishment of new cell lines, improvement of cultural methods, mass cultures</subject><subject>Eukaryotic cell cultures</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>galactose</subject><subject>Galactose - chemistry</subject><subject>glucose</subject><subject>Glucose - chemistry</subject><subject>Glucose - metabolism</subject><subject>glutamate and glucose replacement</subject><subject>Lactic Acid - chemistry</subject><subject>Methods. Procedures. 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J. ; Gòdia, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4576-8d49acc9e6da1336a46488d63b217e7957f0ba4d4d4a49a245792b4e0746273c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Amino Acids - chemistry</topic><topic>Ammonia - chemistry</topic><topic>Animal cells</topic><topic>Animals</topic><topic>arrested cells</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>biphasic culture</topic><topic>Carbon - chemistry</topic><topic>Cell Culture Techniques - methods</topic><topic>Cell Division</topic><topic>Cells, Cultured</topic><topic>Chinese hamster ovary (CHO) cells</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Establishment of new cell lines, improvement of cultural methods, mass cultures</topic><topic>Eukaryotic cell cultures</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>galactose</topic><topic>Galactose - chemistry</topic><topic>glucose</topic><topic>Glucose - chemistry</topic><topic>Glucose - metabolism</topic><topic>glutamate and glucose replacement</topic><topic>Lactic Acid - chemistry</topic><topic>Methods. Procedures. Technologies</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Altamirano, C.</creatorcontrib><creatorcontrib>Cairó, J. 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Cell growth is stopped after this nutrient shift, and the cells can be kept in long‐duration culture at a low growth rate and high viability as compared with a culture strategy based solely on glucose utilization. Moreover, the capability of cells to produce recombinant proteins (t‐PA in this work) can be maintained over the entire period of galactose feeding. From the metabolic point of view, use of a slowly metabolizable carbon source (galactose) introduces important changes in the production of lactate, ammonia, and some amino acids. The use of this metabolic shift enables the generation of biphasic processes, with a first phase with cell growth on glucose and a second stationary phase on galactose, which is particularly suited to perfusion systems. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 351–360, 2001.</abstract><cop>New York</cop><pub>John Wiley & Sons, Inc</pub><pmid>11745163</pmid><doi>10.1002/bit.10096</doi><tpages>10</tpages></addata></record> |
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| subjects | Amino Acids - chemistry Ammonia - chemistry Animal cells Animals arrested cells Biological and medical sciences Biotechnology biphasic culture Carbon - chemistry Cell Culture Techniques - methods Cell Division Cells, Cultured Chinese hamster ovary (CHO) cells CHO Cells Cricetinae Establishment of new cell lines, improvement of cultural methods, mass cultures Eukaryotic cell cultures Fundamental and applied biological sciences. Psychology galactose Galactose - chemistry glucose Glucose - chemistry Glucose - metabolism glutamate and glucose replacement Lactic Acid - chemistry Methods. Procedures. Technologies Time Factors |
| title | Decoupling cell growth and product formation in Chinese hamster ovary cells through metabolic control |
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