The capacity of diploid human lung fibroblasts to produce plasminogen activator was found to vary about 20–fold depending on culture conditions, particularly on the serum used to supplement the growth medium and on the substratum to which the cells are attached. Fibroblasts adapted to produce large amounts of plasminogen activator, by growing for several generation times under conditions which enhance productivity of plasminogen activator, continue to synthesize and secrete the enzyme when transferred to a serum–free medium. Enzyme synthesis is, however, regulated by a negative feedback control exerted by the extracellular enzyme. The feasibility of utilizing fibroblasts for preparation of plasminogen activator was demonstrated on a laboratory scale using batchwise and continuous processes designed to minimize the effects of the feedback control.
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Kadouri, A., Bohak, Z. Production of Plasminogen Activator in Cultures of Normal Human Fibroblasts. Nat Biotechnol 1, 354–358 (1983). https://doi.org/10.1038/nbt0683-354