alkaline phosphatase in mammalian cells. Influence of cell line and culture system upon production kinetics

The growth and productivity of an Sp2/0 cell line, F3bl0, expressing a recombinant antibody (rAb) and BHK21 cells expressing either the same rAb f rom the same plasmids (BHK.IgG) or secreted alkaline phosphatase (SEAP) (BHK.SEAP) were investigated. The F3bl0 line was grown as a single cell suspension. The BHK lines were grown either as suspended natu- ral aggregates or on Cytodex 3 microcarriers. The data for F3bl0 showed that the cell-specific rAb production rate (QSrAb) increased in parallel with increases in the specific growth rate (IX). A similar result was obtained for suspended aggregate cultures of both recombinant BHK cell lines. In contrast, for microcarrier cultures of both BHK cell lines, Qsproduct increased as ~ de- creased. This report shows that the relationship be- tween cell growth and Qspro~uct for the cell lines and products studied is dependent upon the culture proc- ess. In systems where recombinant ceils are growing as a single cell suspension or within a natural suspension aggregrate, Qsproam increased with increases in ~. In such systems, the cells have a rounded morphology. When cells were grown on microcarriers, QSproduct de- creased as Ix increased. Cells growing attached to a sur- face are flat and elongated. The observed differences in the relationship of QSproduc t to Ix are correlated with changes in cell morphology. The relationship between QSproduct and Ix is also affected by the choice of cell line.