Mammalian Cell Bioreactors

Abstract

Mammalian cells are widely used in the production of viral vaccines and therapeutic proteins. Most of those processes employ cells growing in suspension; however, some, especially those in vaccine production, use adherent cells. Stirred‐tank bioreactors are most widely used for mammalian cell culture processes. When a stirred‐tank bioreactor is used for growing adherent cells, a supporting surface for cell attachment is provided by the use of microcarriers or macroporous microcarriers. Alternatively, adherent cells are grown as aggregates in suspension. Fed‐batch culture is commonly practised since it reaches high cell and product concentrations. When a stirred‐tank bioreactor is operated in a continuous mode, it is a common practice to employ a cell retention device for perfusion in order to increase cell and product concentrations. As mammalian cell culture processes are increasingly being used in the manufacturing, one also witnesses an increasing adoption of disposable (or single‐use) cell culture devices. Traditional roller bottles are still often seen. Additionally, multiple flat plates or parallel trays, along with bag type cell growth chambers and even plastic stirred tanks, are used in moderate‐scale production and in the seed culture propagation for large‐scale bioreactors. Those disposable devices offer simplicity in operations and ease process validation in the production of biopharmaceuticals. Recently, some innovative bioreactors developed nearly two decades ago are finding applications in tissue engineering. Furthermore, the demand for high throughput operations in cell culture processing will continue to drive the innovations in bioreactor technology.

Microcarriers for Upscaling Cultured Meat Production

“…In contrast, a higher growth rate was observed on smaller MCs due to increase in shear stress on the larger ones (99,100). Nevertheless, the MC diameter should not be <100 µm as most adherent-dependent cells fail to develop their normal morphology and multiply well on sharply curved surfaces (62,101). It is worth noting here that the development and tailoring of MCs properties for a specific cell type can be very challenging, as traditional material characterization methods used for stiffness, elasticity, topography and roughness measurements are difficult to translate from planar systems to spherical microparticles (19,100).…”

The Interplay Between Cell Adhesion Cues and Curvature of Cell Adherent Alginate Microgels in Multipotent Stem Cell Culture

“…33 The benefit of culturing cells on smaller microgels most likely reaches an endpoint because microcarriers with diameters smaller than 100 mm limit cell adhesion to their surfaces. 34 In addition, the larger dependency of the cell growth rate on the microgel diameter than the dependency of cell differentiation implies that cells at confluency for the differentiation assay were less sensitive to the changes of shear stress, as also confirmed with independency of differentiation level on the direct change of shear stress. It has been known that increased cell-cell contacts leads to the decrease of the cellular sensitivity to the shear stress.…”

Characterization of a quail suspension cell line for production of a fusogenic oncolytic virus

“…The finding that similar virus titers and productivities were also achieved, indicates the usefulness of both bioreactor systems for efficient rVSV‐NDV production. Currently, virus production under cGMP conditions of most manufacturers relies on stainless steel STRs but also on single‐use vessels (Zhou et al, 2010). However, orbitally shaken bioreactors also fulfill these requirements without the need of stirrers, which introduce additional shear stress and raise costs in single‐use applications.…”