Effects of ammonia and lactate on growth, metabolism, and productivity of BHK cells

Cruz, Hélder; Freitas, Catarina; Alves, Paula M.; Moreira, J. L.; Carrondo, Manuel J.T.

doi:10.1016/s0141-0229(00)00151-4

Cited by 156 publications

(125 citation statements)

References 27 publications

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“…7 shows the time courses of Exp.1, a traditional batch culture without feeding. According to model simulation, extra-cellular lysine support cell growth for about 57 hours until the intracellular lysine consumption is triggered and lasts for about another 24 hours, as was found to be 15 hours in Simpson's work [22]. The dynamics of intracellular lysine concentration is qualitatively coincident with the observation of Baydoun et al [35].…”

Section: Resultssupporting

confidence: 67%

“…Therefore, lysine is modeled as a limiting amino acid. As found by Simpson et al [22], there existed a short-term growth after deprivation of single amino acid. The amino acid demand during such a short-term growth period should be met with an intracellular amino acid pool [27].…”

Section: Cell Growth Modelmentioning

confidence: 60%

“…Therefore, the kinetic model proposed in this paper takes lysine, glucose and glutamine as limiting substrates. In addition, the specific growth rate in a conventional unstructured model is usually formulated as Monod type kinetics [13,22,23]. However, such a Monod model is not able to describe the growth lag phase at the beginning of the experiments and after strong environmental perturbation during the cultivations [24,25].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A simple kinetic model for myeloma cell culture with consideration of lysine limitation

Liu

Zeng

et al. 2008

Bioprocess Biosyst Eng

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JournalBioprocess and biosystems engineering AbstractA simple kinetic model is developed to describe the dynamic behavior of myeloma cell growth and cell metabolism. Glucose, glutamine as well as lysine are considered as growth limiting substrates. The cell growth was restricted as soon as the extracellular lysine is exhausted and then intracellular lysine becomes a growth limiting substrate. In addition, a metabolic regulator model together with the Monod model is used to deal with the growth lag phase after inoculation or feeding. By using these models, concentrations of substrates and metabolites, as well as densities of viable and dead cells are quantitatively described. One batch cultivation and two fed-batch cultivations with pulse feeding of nutrients are used to validate the model.

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Section: Resultssupporting

confidence: 67%

Section: Cell Growth Modelmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A simple kinetic model for myeloma cell culture with consideration of lysine limitation

Liu

Zeng

et al. 2008

Bioprocess Biosyst Eng

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“…As can be seen glucose and lactate levels changed markedly over the first 48 h. At the end of the cultivation period glucose level was 11.4 mM while lactate level was equal to 12.3 mM and glutamine and ammonia concentrations were equal to 0.14 and 1.96 mM, respectively. Lactate was below inhibitory level of 22 mM as reported for stirred BHK 21A culture (Cruz et al 2000) while ammonium was in the concentration range which already tends to a growth reduction of BHK cells grown on microcarriers (Butler and Spier 1984).…”

Section: Cell Culture Growthmentioning

confidence: 54%

BHK 21 C13 cells for Aujeszky’s disease virus production using the multiple harvest process

et al. 2004

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Production of Aujeszky's disease virus (ADV) from BHK 21 C13 suspension cells using a simple harvest and multiple harvest process mode was examined. We studied growth kinetics of BHK 21 C31 cells in 750 ml spinner flask containing 500 ml of culture medium. In the simple harvest process of ADV production, 425 ml of virus harvest was obtained with a virus titer of 10 6.4 TCID 50 ml À1 which corresponds to 10,676 doses of vaccine. The multiple harvest process resulted in 850 ml of virus harvest with a virus titer of 10 6.5 TCID 50 ml À1 corresponding to 26,877 AD vaccine doses. In conclusion, the multiple harvest process mode using BHK 21 C13 can be considered as a favorable process to produce ADV.

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“…Among the metabolites involved in insect cell cultivation, glucose, lactate and ammonia emerge as important ones. Glucose has been indicated as one of the main energy sources for insect cells (Drugmand et al 2012), while lactate and ammonia have been demonstrated to adversely affect them because of the toxic effects they produce when they accumulate in the culture medium (Cruz et al 2000). Metabolic profiles vary among insect cells lines.…”

Section: Introductionmentioning

confidence: 99%

Characterization of growth and Oryctes rhinoceros nudivirus production in attached cultures of the DSIR-HA-1179 coleopteran insect cell line

et al. 2013

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The DSIR-HA-1179 coleopteran cell line is a susceptible and permissive host to the Oryctes rhinoceros nudivirus (OrNV), which has been used as a biocontrol agent against the coconut rhinoceros beetle (Oryctes rhinoceros); a pest of palms in the Asia-Pacific region. However, little is known about growth and metabolism of this cell line, knowledge of which is necessary to develop an in vitro large-scale OrNV production process. The strong anchoragedependent characteristics of the cell line, its particular fragility and its tendency to form dense clumps when manipulated, are the most likely reasons that have precluded further development of the cell line. In order to characterize DSIR-HA-1179 cells, there was first a need for a reliable technique to count the cells. A homogenous cell suspension suitable for enumeration could be produced by treatment with TrypLE Express TM with optimum mean time for cell release calculated as 30 min. The cell line was adapted to grow in four serum-supplemented culture media namely TC-100, IPL-41, Sf-900 II and Sf-900 III and cell growth, glucose consumption, lactate and ammonia production were assessed from static-batch cultures. The maximum viable cell density was reached in Sf-900 II (17.9 9 10 5 cells/ml), with the maximum specific growth rate observed in this culture medium as well (0.0074 h -1 ). Higher production of OrNV was observed in IPL-41 and TC-100 (4.1 9 10 7 TCID 50 /ml) than in cultures infected in Sf-900 III (2.0 9 10 7 TCID 50 /ml) and Sf-900 II (1.4 9 10 7 TCID 50 /ml). At the end of the growth period, glucose was completely consumed in cultures grown in TC-100, while remained in excess in the other three culture media. The cell line produced lactate and ammonia to very low levels in the TC-100 culture medium which is a promising aspect for its cultivation at large-scale.

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Effects of ammonia and lactate on growth, metabolism, and productivity of BHK cells

Cited by 156 publications

References 27 publications

A simple kinetic model for myeloma cell culture with consideration of lysine limitation

A simple kinetic model for myeloma cell culture with consideration of lysine limitation

BHK 21 C13 cells for Aujeszky’s disease virus production using the multiple harvest process

Characterization of growth and Oryctes rhinoceros nudivirus production in attached cultures of the DSIR-HA-1179 coleopteran insect cell line

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