CONTINUOUS PRODUCTION OF TPA BY RECOMBINA NT BHK CELLS IN A MICRO-FILTRATION HOLLOW-FIBER BIOREACTOR

Continuous cultivation of recombinant Baby Hamster Kidney (BHK) cells producing tissue plasminogen activator (tPA) was carried out in a micr o-filtration hollow fiber (MFHF) bioreactor using Dulbecco's Modified Eagle's medium with serum. Stable, continuous cultivation for 66 d was possible, compared with a stoppage of cultivation at 40 d in the case of an ultra-filtration hollow fiber (UFHF) bioreactor. After the cell s were fully grown, the serum concentration was decreased from 5% to 1 %, but the tPA productivity remained at the same level continuously. T he mean tPA concentration was 17.1 mg/l and the mean daily tPA product ion was 590 mg/d. The tPA productivity was 150 mg/d/m(2) in the case o f the MFHF bioreactor. As the medium in the MFHF bioreactor was evenly supplied from the intra-capillary to the extra-capillary space, the t PA productivity of this bioreactor was 16% better than that of the UFH F type. The simplified culture system of the MFHF bioreactor make it s uitable for commercial-scale tPA production.