Fluid shear stress induction of the transcriptional activator c-fos in human and bovine endothelial cells, HeLa, and Chinese hamster ovary cells

Ranjan, V.; Waterbury, Raymond; Xiao, Zeshuai; Diamond, Scott L.

doi:10.1002/(sici)1097-0290(19960220)49:4<383::aid-bit4>3.0.co;2-l

Cited by 32 publications

(14 citation statements)

References 37 publications

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“…Unfortunately, the authors do not know of any studies in which the force necessary (applied in a normal direction) to remove cells from a microcarrier have been measured or calculated. Probably the closest related study is that of Ranjan et al (1996) in which well-defined shear stress was applied to CHO cells attached to a glass surface. In those studies, it was shown that, roughly speaking, CHO cells responded to shear stress in a manner similar to that of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Cell‐Microcarrier Adhesion to Gas‐Liquid Interfaces and Foam

Bauer

Hancock

Rathman

et al. 2000

Biotechnology Progress

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The interaction of microcarriers, both with and without cells attached, with gas bubbles was studied. These studies consisted of qualitative microscopic observations of microcarriers with bubbles, quantitative measurements of microcarrier entrapment in foam, and quantitative measurements of the effect of bubble rupture at gas-medium interfaces. Ten different "protective additives" were evaluated for their ability to change the dynamic surface tension of the culture media and to prevent microcarrier adhesion to air bubbles during gas sparging and to prevent entrapment in the foam layer. These studies indicate that microcarriers, with and without cells, readily attach to gas-medium interfaces; yet unlike suspended cells, cells attached to microcarriers are not damaged by bubble ruptures at gas-medium interfaces. Only one surfactant was found to substantially prevent microcarrier entrapment in the foam layer; however, this surfactant was toxic to cells. No correlation was observed between surface tension and the prevention of microcarrier adhesion to gas-liquid interfaces. It is suggested that cell damage as a result of sparging in microcarrier cultures is the result of cells, attached to microcarriers, attaching to rising bubbles and then detaching from the microcarrier as this combination rises through the medium. It is further suggested that the hydrodynamic drag force of the rising microcarrier is sufficiently high to remove the bubble-attached cell from the microcarrier.

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Section: Discussionmentioning

confidence: 99%

Cell‐Microcarrier Adhesion to Gas‐Liquid Interfaces and Foam

Bauer

Hancock

Rathman

et al. 2000

Biotechnology Progress

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“…C-fos protein, a transcriptional activator, can be induced at 25 dyn/cm 2 (2.5 N/m 2 ) in CHO cells (Ranjan et al 1995). (6) Cell cycle Motobu et al (1998) found that more than 60% of CHO cells, which grew at the bottom of a flow chamber, were arrested in the G0/G1 phase after exposure to shear stress of 0.02 or 0.082 N/m 2 for 24 h.…”

Section: Sub-lethal Effectmentioning

confidence: 99%

The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding

Hu¹,

2011

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Suspension animal cell culture is now routinely scaled up to bioreactors on the order of 10,000 L, and greater, to meet commercial demand. However, the concern of the 'shear sensitivity' of animal cells still remains, not only within the bioreactor, but also in the downstream processing. As the productivities continue to increase, titer of ~10 g/L are now reported with cell densities greater than 2 × 10(7) cells/mL. Such high, and potentially higher cell densities will inevitably translate to increased demand in mass transfer and mixing. In addition, achieving productivity gains in both the upstream stage and downstream processes can subject the cells to aggressive environments such as those involving hydrodynamic stresses. The perception of 'shear sensitivity' has historically put an arbitrary upper limit on agitation and aeration in bioreactor operation; however, as cell densities and productivities continue to increase, mass transfer requirements can exceed those imposed by these arbitrary low limits. Therefore, a better understanding of how animal cells, used to produce therapeutic products, respond to hydrodynamic forces in both qualitative and quantitative ways will allow an experimentally based, higher, "upper limit" to be created to guide the design and operation of future commercial, large scale bioreactors. With respect to downstream hydrodynamic conditions, situations have already been achieved in which practical limits with respect to hydrodynamic forces have been experienced. This review mainly focuses on publications from both the academy and industry regarding the effect of hydrodynamic forces on industrially relevant animal cells, and not on the actual scale-up of bioreactors. A summary of implications and remaining challenges will also be presented.

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“…This is significantly lower than the level required to lyze similar cell lines. Of bioprocess relevant cell lines, Ranjan et al (1996) found an induction of transcriptional activator c-fos when CHO cells were subjected to 2.5 N/m 2 (6.2 Â 10 3 W/m 3 ) shear force for 1 h. Ludwig et al (1992) observed morphologically that the time for adherent BHK-21 cells to spread after division increased when the cells were exposed to 4.5 N/m 2 (2.0 Â 10 4 W/m 3 ). Al-Rubeai et al (1995) detected apoptosis of hybridoma cells at volumetric average energy dissipation of 1.87 Â 10 3 W/m 3 .…”

Section: Introductionmentioning

confidence: 99%

Physiological responses of CHO cells to repetitive hydrodynamic stress

Godoy-Silva

Chalmers

Casnocha

et al. 2009

Biotech & Bioengineering

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A majority of the previous investigations on the hydrodynamic sensitivity of mammalian cells have focused on lethal effects as determined by cell death or lysis. In this study, we investigated the effect of hydrodynamic stress on CHO cells in a fed-batch process using a previously reported system which subjects cells to repetitive, high levels of hydrodynamic stress, quantified by energy dissipation rate (EDR). The results indicated that cell growth and monoclonal antibody production of the test cells were very resistant to the hydrodynamic stress. Compared to the control, no significant variation was observed at the highest EDR tested, 6.4 x 10(6) W/m(3). Most product quality attributes were not affected by intense hydrodynamic stress either. The only significant impact was on glycosylation. A shift of glycosylation pattern was observed at EDR levels at or higher than 6.0 x 10(4) W/m(3), which is two orders of magnitude lower than the EDR where physical cell damage, as measured by lactate dehydrogenase release, was observed. While not as extensively investigated, a second monoclonal antibody produced in a different CHO clone exhibited the same glycosylation change at an intensive EDR, 2.9 x 10(5) W/m(3). Conversely, a low EDR of 0.9 x 10(2) W/m(3) had no effect on the glycosylation pattern. As 6.0 x 10(4) W/m(3), the lowest EDR that triggers the glycosylation shift, is about one order of magnitude higher than the estimated, maximum EDR in typically operated, large-scale stirred tank bioreactors, further studies in a lower EDR range of 1 x 10(3)-6.0 x 10(4) W/m(3) are needed to assess the glycosylation shift effect under typical large-scale bioreactor operation conditions. Follow-up studies in stirred tanks are also needed to confirm the glycosylation shift effect and to validate the repetitive hydrodynamic stress model.

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Fluid shear stress induction of the transcriptional activator c-fos in human and bovine endothelial cells, HeLa, and Chinese hamster ovary cells

Cited by 32 publications

References 37 publications

Cell‐Microcarrier Adhesion to Gas‐Liquid Interfaces and Foam

Cell‐Microcarrier Adhesion to Gas‐Liquid Interfaces and Foam

The potential of hydrodynamic damage to animal cells of industrial relevance: current understanding

Physiological responses of CHO cells to repetitive hydrodynamic stress

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