DYNAMICS OF RECOMBINANT PROTEIN-PRODUCTION BY MAMMALIAN-CELLS IN IMMOBILIZED PERFUSION CULTURE

In spite of the generally stable nature of immobilized perfusion cultu re, its profile of target protein production frequently shows variatio ns. This might be explained by the drift in the metabolism of cultured cells. To address this issue, we performed a set of four Opticell bio reactor 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 me tabolism was fluctuated with a parallel fluctuation in the recombinant protein productivity (RPP). The mean productivity of recombinant PCGF X was determined to be about 1.0 mg day(-1) for all the cultures. The statistical analysis revealed a significant correlation between the la ctate production rate (LPR) and RPP in two cultures. A significant cor relation was further Sound between average OCR and RPP in another cult ure where OCR was exceptionally lowered under serum-free conditions. N o parameter significantly correlated with RPP in the remaining one cul ture; 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.