Small Microcarrier Aggregates Yield High Cell Density

A commonly held belief has been that microcarrier-cell aggregates (clumps) leads to necrosis of the cells in the core of the aggregate. We, and others, have results that contradict that belief (1-4). Another commonly held belief is that microcarriers below a given size (approximately 75 microns) deter or disallow cell attachment. In our studies (a) we demonstrated that cell yields can be greatly increased by utilizing very small spheres (38-63pm), (b) we showed further that the high cell densities were achieved by virtue of rapid cell attachment to the microcarriers with concomitant microcarrier aggregation and high cell growth and (c) we demonstrated that cells growing in high cell density remained metabolically active and produced high levels of at least one commercially-relevant biological. On a per cell basis, cells growing in high-density, small-microcarrier cultures synthesized protein and produced infectious bovine rhinotracheitis virus as efficiently as cells in monolayer culture.