Influence of hydrodynamic shear stress on microcarrier-attached cell growth: Cell line dependency and surfactant protection

Wu, Suh-Chin

doi:10.1007/s004490050663

Cited by 31 publications

(18 citation statements)

References 12 publications

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“…In agreement with the findings of Wu 40 for Vero cells, an increase in adhesion areas with increasing fluid dynamic forces was observed for MDCK cells, and most likely reflects a general property of anchorage dependent cell lines.…”

Section: Modelssupporting

confidence: 88%

Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures

Böck

Sann

Schulze‐Horsel

et al. 2009

Biotechnology Progress

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An assay for measuring the number of adherent cells on microcarriers that is independent from dilution errors in sample preparation was used to investigate attachment dynamics and cell growth. It could be shown that the recovery of seeded cells is a function of the specific rates of cell attachment and cell death, and finally a function of the initial cell-to-bead ratio. An unstructured, segregated population balance model was developed that considers individual classes of microcarriers covered by 1-220 cells/bead. The model describes the distribution of initially attached cells and their growth in a microcarrier system. The model distinguishes between subpopulations of dividing and nondividing cells and describes in a detailed way cell attachment, cell growth, density-dependent growth inhibition, and basic metabolism of Madin-Darby canine kidney cells used in influenza vaccine manufacturing. To obtain a model approach that is suitable for process control applications, a reduced growth model without cell subpopulations, but with a formulation of the specific cell growth rate as a function of the initial cell distribution on microcarriers after seeding was developed. With both model approaches, the fraction of growth-inhibited cells could be predicted. Simulation results of two cultivations with a different number of initially seeded cells showed that the growth kinetics of adherent cells at the given cultivation conditions is mainly determined by the range of disparity in the initial distribution of cells on microcarriers after attachment.

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Section: Modelssupporting

confidence: 88%

Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures

Böck

Sann

Schulze‐Horsel

et al. 2009

Biotechnology Progress

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show abstract

“…Although BHK cells were proved to be more resistant to fluidmechanical forces in microcarrier cultures (23) and are easily adapted to grow as a single cell suspension, BHK cells are not acceptable to produce human vaccines. Differences between Vero and BHK cells were again demonstrated in this study.…”

Section: Discussionmentioning

confidence: 98%

Stationary and Microcarrier Cell Culture Processes for Propagating Japanese Encephalitis Virus

Wu¹,

Huang²

2002

Biotechnology Progress

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Inactivated mouse-brain-derived vaccines for Japanese encephalitis virus (JEV) have been used for many years. Recently, attempts have been made to employ cultured Vero cells to replace mouse brain tissues for developing cell-culture-derived vaccines that will be more suitable for worldwide usage. In this study, JEV replication processes in Vero and BHK cells and between stationary and microcarrier culture systems were investigated. Our results demonstrated that a stationary Vero cell culture system produced higher viral titers of JEV, including the Beijin-1 vaccine strain and the attenuated strain CH2195LA, than microcarrier culture did. BHK cells showed less significant differences in their replication kinetics between stationary and microcarrier cultures. Reducing serum concentration during infection led to an overall decrease of JEV production in Vero cells but an increase in BHK cells. By establishing a complete serum-free Vero cell culture, the microcarrier system resulted in a more than 4-log lowered yield compared to that of the stationary culture for JEV production. Thus, the stationary culture is the most efficient system for JEV production from cultured Vero cells.

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“…This ®nding may account for why stimulation of JEV burst size by shear force was not observed in BHK-21 cells. However, since BHK-21 cells are less sensitive to shear stress than Vero cells [10], the inherent cell-speci®c characteristics may also account for the unique feature of stress-enhanced JEV production in Vero cells.…”

Section: Discussionmentioning

confidence: 99%

Hydrodynamic shear forces increase Japanese encephalitis virus production from microcarrier-grown Vero cells

Huang

2000

Bioprocess Engineering

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Understanding the effect of hydrodynamic shear forces on microcarrier-attached cells is critical in several viral vaccine production processes, owing to that only the anchorage-dependent cells can be used for virus propagation in cultures. This study demonstrated that increasing the hydrodynamic shear forces in microcarrier cultures can increase the production of a vaccine strain of Japanese encephalitis virus (on a per cell basis) in Vero cells but not BHK-21. The shear force-enhanced JEV production were highly effective at around 2±3 d post infection and required the concentration of fetal bovine serum supplemented in medium above 2.5%. To our knowledge, this study reports for the ®rst time that increasing the hydrodynamic shear forces on microcarriergrown cells increases virus production in agitated bioreactor cultures.

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Influence of hydrodynamic shear stress on microcarrier-attached cell growth: Cell line dependency and surfactant protection

Cited by 31 publications

References 12 publications

Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures

Growth behavior of number distributed adherent MDCK cells for optimization in microcarrier cultures

Stationary and Microcarrier Cell Culture Processes for Propagating Japanese Encephalitis Virus

Hydrodynamic shear forces increase Japanese encephalitis virus production from microcarrier-grown Vero cells

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