TISSUE-PLASMINOGEN ACTIVATOR (T-PA) PRODUCTION BY A HIGH-DENSITY CULTURE OF WEAKLY ADHERENT HUMAN EMBRYONIC KIDNEY-CELLS USING A POLYURETHANE-FOAM PACKED-BED CULTURE SYSTEM

Weakly adherent cells of the 293 line attached well to the internal su rface of polyurethane foam (PUF) and grew to the high density of 6.83 x 10(7) cells/cm(3) PUF in stationary culture. The maximum productivit y of tissue plasminogen activator (t-PA) was 0.158 IU/10(6) cells per day. The productivity decreased at the stationary phase of cell growth , so we designed a PUF-plate packed-bed culture system for high densit y culture and continuous production of t-PA. A maximal cell density of 3.24 x 10(7) cells/cm(3) PUF and a t-PA productivity of 0.326 IU/10(6 )cells per day were obtained in 25-day perfusion cultures. Although th e cell density decreased to half that in PUF stationary culture, the t -PA productivity increased twofold and was maintained for 25 culture d ays.