Optimization of fed-batch culture of hybridoma cells using dynamic programming: single and multi feed cases

Tremblay, Mireille; Perrier, Michel; Chavarie, C.; Archambault, Jean

doi:10.1007/bf00369551

Cited by 100 publications

(57 citation statements)

References 8 publications

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“…This has been observed for cells cultivated in batch (Ramirez and Mutharasan, 1990), fed-batch (de Tremblay et al, 1993;Robinson et al, 1994), chemostat (Boraston et al, 1984), and perfusion modes (Al-Rubeai et al, 1992;Banik and Heath, 1995;Batt et al, 1990;de la Broise et al, 1991;Johnson et al, 1996;Hansen et al, 1993;Park and Ryu, 1994;Tokashiki and Takamatsu, 1993;Trampler et al, 1994), as well as in cells treated with cell-cycle blocking agents (Al-Rubeai and Emery, 1990;Jayme, 1991;Mercille and Massie, 1998;Oh et al, 1995;Øyaas et al, 1994a,b;Reddy and Miller, 1994;Suzuki and Ollis, 1990;Takahachi et al, 1994). Indeed, specific antibody production has been shown to be cell cycle dependent and optimum in the G 1 and/or G 2 /M phase (Cazzador and Mariani, 1993;Kromenaker and Srienc, 1991;Linardos et al, 1992;Richieri et al, 1991;Suzuki and Ollis, 1989).…”

Section: Introductionmentioning

confidence: 85%

Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions

Mercille¹,

Massie²

1999

Biotechnol. Bioeng.

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Section: Introductionmentioning

confidence: 85%

Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions

Mercille¹,

Massie²

1999

Biotechnol. Bioeng.

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“…Both cell lines tested negative for mycoplasma contamination using a Hoechst staining and coculturing detection assay (ATCC quality control methods for cell fines, first edition, 1985, pp. [12][13][14][15].…”

Section: Cell Linesmentioning

confidence: 99%

Induction of apoptosis in nutrient‐deprived cultures of hybridoma and myeloma cells

Mercille

Massie²

1994

Biotech & Bioengineering

276

213

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In the present study, cell death was investigated in cultures of NS/0 myelomas and SP2/0-derived D5 hybridomas through morphological examination of cells stained with acridine orange and ethidium bromide. The relative contribution of elevated levels of lactic acid and ammonia, as well as deprivation of glutamine, cystine, and glucose on the induction of necrosis or apoptosis, was investigated. In batch culture of D5 hybridoma cells, induction of apoptotic cell death correlated with the exhaustion of glutamine, while in the case of NS/0 myelomas, it coincided with exhaustion of cystine. To determine whether limiting nutrients were the actual triggering factors for apoptosis in batch culture, exponentially growing cells were resuspended in glutamine or cystine-free media. Within 30 to 40 h, viability decreased to 50% and the nonviable cell population displayed typical apoptotic morphology, with crescents of condensed chromatin around the periphery of the nucleus, or with the entire nucleus present as one or a group of featureless, brightly staining spherical beads. Similarly, D5 hybridomas and NS/0 myelomas cultivated in glucose-free medium died mainly from apoptosis. Cells were also cultivated in fresh medium supplemented with elevated concentrations of ammonia (3.0 mM) and/or lactate (35 mM, 50 mM). This resulted in decreased viabilities and necrotic death in both cell lines. From these results, we conclude that D5 hybridomas and NS/0 myelomas deprived of essential nutrients die by apoptosis, whereas incubation in the presence of elevated levels of metabolic byproducts such as ammonia and lactate will induce necrotic cell death in these cells.

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“…Operation of the cell culture process in either fed-batch or perfusion modes is another way of enhancing cell density and thus productivity (Detremblay et al, 1992;Lee et al, 2005;Nguang et al, 2001;Trampler et al, 1994). With these modes of operation, it is possible to reach higher cell density and prolonged sustainability of cell viability.…”

Section: Motivationmentioning

confidence: 99%

Dynamic Modeling of Apoptosis and its Interaction with Cell Growth in Mammalian Cell Culture

Meshram¹,

Naderi²,

Wei³

et al. 2011

IFAC Proceedings Volumes

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Optimization of fed-batch culture of hybridoma cells using dynamic programming: single and multi feed cases

Cited by 100 publications

References 8 publications

Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions

Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions

Induction of apoptosis in nutrient‐deprived cultures of hybridoma and myeloma cells

Dynamic Modeling of Apoptosis and its Interaction with Cell Growth in Mammalian Cell Culture

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