Dynamics of recombinant protein production by mammalian cells in immobilized perfusion culture

摘要

In spite of the generally stable nature of immobilized perfusion culture, its profile of target protein production frequently shows variations. This might be explained by the drift in the metabolism of cultured cells. To address this issue, we performed a set of four Opticell bioreactor cultures producing recombinant anticogulant protein PCGFX. All the cultures lasted 40-50 days with the oxygen consumption rate (OCR) mostly around 10 mu mol min(-1); nevertheless, glucose and lactate metabolism was fluctuated with a parallel fluctuation in the recombinant protein productivity (RPP). The mean productivity of recombinant PCGFX was determined to be about 1.0 mg day(-1) for all the cultures. The statistical analysis revealed a significant correlation between the lactate production rate (LPR) and RPP in two cultures. A significant correlation was further Sound between average OCR and RPP in another culture where OCR was exceptionally lowered under serum-free conditions. No parameter significantly correlated with RPP in the remaining one culture; thus, the overt drift of RPP resulted at least partly, from that of the cell metabolic activity and the present data should be helpful to explore a strategy for maximizing productivity. (C) 1998 Elsevier Science Inc. [References: 25]