Structured Model of VERO Cells Metabolism in a Fixed-Bed Bioreactor

Abstract

In this work, a structured mathematical model of the VERvet Origin (VERO) cell metabolism in a fixed-bed bioreactor is developed. Mass balance equations for the extra-and intracellular species are written considering the main pathways of the animal cell metabolism. From the model equations, an undetermined set of equations relating the consumption or production velocities of the extracellular species and the velocities of the metabolic reactions can be developed. The monitoring of a reference cell culture enables to transform this undetermined set of equations in a determined one. The resolution of this determined set of equations enables to analyze and characterize the cell metabolism. From the model and the cell metabolism characterization, a monitoring tool is developed to simulate the time evolution of the species concentrations when the time evolution of the cell concentration is known. This simulation tool is used to simulate five experimental cell cultures. The comparison of the experimentally determined and computed time evolutions of the species concentrations enables to validate the developed monitoring tool. The validated monitoring tool can be used to optimize the operating conditions of the culture, as the medium feeding rate, the range of the species concentrations.

Evaluation of the Single‐Use Fixed‐Bed Bioreactors in Scalable Virus Production

“…Fixed‐bed fibers have proven to be efficient for different kinds of adherent cells and even more precisely, there are no publications describing cells that lack the ability for growth in the fixed‐bed bioreactor. The most frequently used cells in virus production have been human embryonic kidney (HEK)‐derived cells, [ 5–10,27,26 ] but many other cell types such as Vero, [ 11,38,39,12,28,29 ] MRC‐5, [ 11 ] A549, [ 9,12 ] Chinese hamster ovary cell line, [ 40 ] bovine herpesvirus (BHV), [ 13 ] chicken embryonic fibroblasts (CEF), Madin‐Darby canine kidney cell line, [ 28 ] Sf9, [ 30 ] or Madin‐Darby bovine kidney (MDBK) [ 12 ] cells have been successfully cultivated in the fixed‐bed bioreactors. Cells anchor themselves onto the fiber network and start to grow on adherently, making layers (Figure 1B.…”

“…The velocities of the cell metabolic reactions can be modeled based on the experimental cell culture data and mathematical predictions to create a validated monitoring tool for process optimization and control. [ 38,39 ]…”

Segregated Model of Adherent Cell Culture in a Fixed-Bed Bioreactor

“…The Monod constants ( ) are identified from a review of the literature and the kinetic constants of the cell metabolic rates ( ) have been identified in a previous work where the metabolism is characterized by a network flux (Gelbgras et al 2010b). These constants are given in Table 10.…”

Optimizing and developing a scalable, chemically defined, animal component-free lentiviral vector production process in a fixed-bed bioreactor

“…The iCELLis platform has been used for a wide range of applications such as viral vaccines, 16 poxvirus production on chicken embryo fibroblasts, 17 VERO cell line metabolism studies, 18 and culture of insect cells. 19 However, the platform is routinely used for virus production such as adenovirus, 20 retrovirus, 21 , 22 AAV, 23 , 24 and LVVs 25 , 26 using mainly transient transfection of adherent cell lines such as HEK293, HEK293T, or HEK293T/17 cells.…”