Application of hypoosmolar medium to fed-batch culture of hybridoma cells for improvement of culture longevity

Cell death in mammalian cell culture: molecular mechanisms and cell line engineering strategies

“…In fed-batch, perfusion and chemostat cultures the situation is more complex since nutrients are constantly replenished and in some cases metabolites are removed. Cells can undergo apoptosis when nutrients are in critically low concentration or in response to various environmental stress factors such as high osmolality, pH fluctuations, oxygen gradients and deprivation due to insufficient mixing at high cell densities and potential generation of reactive oxygen species Singh et al 1994;Al-Rubeai et al 1995a;Simpson et al 1998;Singh and Al-Rubeai 1998;Ryu and Lee 1999). Also, exposure to increasing hydrodynamic forces by bubble bursting at the liquid surface, gas sparging, liquid flow or gas entrainment and energy dissipation of the impeller stream can induce apoptosis (Al-Rubeai et al 1995a;Chisti 2000).…”

Phosphate feeding improves high-cell-concentration NS0 myeloma culture performance for monoclonal antibody production

“…Recent years have witnessed intensive bioprocessing research to enhance productivity (Bedard et al, 1997;Bibila and Robinson, 1995;Bibila et al, 1994;Bushell et al, 1994;DiStefano et al, 1996;Honda et al, 1998;Lenas et al, 1997;Robinson et al, 1994Robinson et al, , 1995Ryu and Lee, 1999;Xie and Wang, 1996;Zhou et al, 1995Zhou et al, , 1997a. Notable is the relentless pursuit of either a perfusion or fed-batch process that results in an increased cell concentration and extended culture lifetime.…”

5.3 Nutrient Media for Cell Culture Technology

“…This strategy has significantly increased cellular concentrations, the cell integral, and the recombinant protein production in CHO cells [65], hybridomas [66], myeloma [67], and 293 human kidney cells [68]. However, despite its effectiveness, the high cost, which may involve feeding all the nutrients of the medium and the high risk of increasing the osmolality of the medium, may be factors against the use of these feeds.…”