Combination of dextran sulfate and recombinant trypsin on aggregation of Chinese hamster ovary cells

In laboratory scale therapeutical protein production, cell clumps form typically in shake flasks, which hinders cell growth and decreases protein yield. To minimize clumps during the culture of Chinese hamster ovary cells, we employed the combination of two reagents, dextran sulfate (DS) and recombinant trypsin (r-trypsin). Our results showed that both DS and r-trypsin could diminish cell aggregation when adding them respectively, but clumps were still noticed obviously. In order to further mitigate cell agglomerate, a combination of 1.2 g/L DS and 8.0 mg/L r-trypsin was employed and no clumps were found under the bright field microscope. Strikingly, the highest viable cell density of combination group was increased from 5.12 × 10⁶ to 7.13 × 10⁶ cells/mL, while the integral of viable cells concentration was raised from 35.13 × 10⁶ to 60.87 × 10⁶ cells·days/mL, and the culture period was prolonged by 4 days. In addition, the antibody integrity was maintained in the combination group compared with that of the control.