Large-scale insect and plant cell culture

Abstract

Currently, insect and plant cell cultures are not widely used to make products of commercial interest, largely because the development of large-scale cultivation methods is still in its infancy. With the advances made over the past year, some of the limitations associated with scale-up of these two types of expression system have been addressed. Increasing the oxygen supply and the concentration of various nutrients supplied to insect cells after infection has enabled high specific protein production to be maintained to higher cell densities than ever before, improving overall volumetric yields. Detailed work has focused on the capacity of insect cells to carry out complex post-translational modifications; however, as yet, evidence is conflicting as to the extent of protein processing and complex glycosylation possible in infected cells. In plant cell culture, the accepted axioms concerning large-scale culture have been re-examined. Recent studies have assessed culture at high cell densities and the constraints in reactor design resulting from the 'shear sensitivity' of plant cells. Results show that, as cell densities increase, alterations occur in the pathways of secondary metabolism, leading to decreases in specific productivity. The use of nutrient supplements and a medium cycling strategy shows promise for increasing and sustaining product formation. Furthermore, the importance of dissolved gas composition has been clearly demonstrated by use of a gas recirculation reactor. Reports of taxol and vindoline production in vitro demonstrate the potential and the necessity for further research in scale-up of plant cell culture.