Molecular Farming Using Bioreactor-Based Plant Cell Suspension Cultures for Recombinant Protein Production

On the way to commercializing plant cell culture platform for biopharmaceuticals: present status and prospect

“…Enhanced protein productivity can be achieved through optimization of bioreactor culture conditions and development of advanced bioreactor culture strategies [31,40,119]. With the optimization of various operating conditions in a batch culture bioreactor (e.g., agitation speed, aeration rate, pH and dissolved oxygen, higher protein yields than those obtained from shake flasks were achieved [108,120].…”

“…However, only a few studies related to advanced culture strategies for plant cell culture have been reported and most of them directed to the production of secondary metabolites [31]. More information on adoption of advanced bioreactor culture strategies for enhanced plant cell-based production can be found in some recent reviews [31,40,119]. …”

“…Although plant cells are readily cultured in most standard bioreactors, and those well-established principles for the cultures of microbial and mammalian cells also apply to plant cell culture, the transition from shake flasks to bioreactors is still complicated and problematic; poor cell growth and low protein production have been reported when the plant cell culture was scaled up in bioreactors [149,150]. The engineering considerations of scaling up plant cell culture and important features of various types of bioreactors have been well reviewed by Huang and McDonald recently [40,119]. …”

“…Two distinctive properties of plant cell culture that call for a special consideration in bioreactor process development include large cell size and complex morphology [31,119]. Plant cells (20–50 μm in diameter and 100–500 μm in length) are significantly larger than bacteria (<1 μm in diameter), yeasts (3–5 μm in diameter) and mammalian cells (10–100 μm in diameter), with a large intracellular vacuole accounting for up to 90% of the cell volume and a rigid, inflexible cellulose-based cell wall [40,151].…”

“…The sizes of cell aggregate are dependent on plant species, medium composition, inoculum, cell growth stage and culture conditions [119]. On the one hand, formation of moderate cell aggregates (e.g., 100–1000 μm), known as self-immobilization of cells, may protect the shear-sensitive plant cells from shear damage and enhance sedimentation rates of the cultured cells, thus facilitating media exchange as well as in situ recovery of culture broth.…”