Cell-cell Adhesion and Aggregation: Influence on the Growth Behavior of CHO Cells

The influence of cell-cell adhesion on the growth behavior of Chinese hamster ovary (CHO) cells in suspension culture was investigated. CHO cells form aggregates under suboptimal growth conditions. Clusters are formed around decaying and dead cells. The deoxyribonucleic acid (DNA) released from these cells was found to mediate the cells was found to mediate the cell-cell adhesion. Cluster formation dramatically influenced the growth behavior of the cells. First, cells within aggregates showed a strongly reduced specific proliferation rate, and second, shear forces exerted on large aggregates caused a considerable higher specific death rate than those exerted on single cells. These factors led to a reduction of the specific growth rate up to 50%. This decrease could be avoided by addition of DNase 1 to the medium. It is shown that the separate determination of the specific proliferation and death rates is not feasible with state-of-the-art methods. To achieve a more profound and precise description of the growth pattern of animal cells, we propose an extended Monod model and describe the relevant methods.