Authors: T Tharmalingam K Sunley M Spearman M Butler
Publish Date: 2011/04/07
Volume: 49, Issue: 3, Pages: 263-276
Abstract
Macroporous microcarriers entrap cells in a mesh network allowing growth to high densities and protect them from high shear forces in stirred bioreactor cultures We report the growth of Chinese hamster ovary CHO cells producing either recombinant human betainterferon βIFN or recombinant human tissueplasminogen activator tPA in suspension or embedded in macroporous microcarriers Cytopore 1 or 2 The microcarriers enhanced the volumetric production of both βIFN and tPA by up to 25 fold compared to equivalent suspension cultures of CHO cells Under each condition the cell specific productivity Q P was determined as units of product/cell per day based upon immunological assays Cells grown in Cytopore 1 microcarriers showed an increase in Q P with increasing cell densities up to a threshold of 1 × 108 cells/ml At this point the specific productivity was 25 fold higher than equivalent cells grown in suspension but cell densities above this threshold did not enhance Q P any further A positive linear correlation r 2 = 093 was determined between the specific productivity of each recombinant protein and the corresponding cell density for CHO cells grown in Cytopore 2 cultures With a cell density range of 25 × 106 to 3 × 108 cells/ml within the microcarriers there was a proportional increase in the specific productivity The highest specific productivity measured from the microcarrier cultures was ×5 that of suspension cultures The relationship between specific productivity and cell density within the microcarriers leads to higher yields of recombinant proteins in this culture system This could be attributed to the environment within the microcarrier matrix that may influence the state of cells that could affect protein synthesis or secretion
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