BIOCHEMICAL CONTROL OF MICROCARRIER PROCESSES

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The main objective of this program is to develop vastly improved microcarrier beads for use in commercial applications. Mammalian cell anchorage materials (microcarriers and roller bottles) are in large-scale use in the manufacture of viral vaccines for humans and animals, representing a $5 million market. The Phase II studies will examine the production and utilization of matrix components and how these influence the behavior of cells. Specifically, we will: (1) measure the production of noncollagenous extracellular matrix (ECM) components (fibronectin, laminin, and thrmbospondin) expressed by fibroblasts and epithelial cells grown on one experimental and six substrates currently used in large-scale cell cultivation; (2) determine the influence of these substrates on the expression of cell surface receptors; (3) examine the elaboration of plasminogen-dependent and plasminogen-independent enzymes to determine their influence on the structure and/or function of endogenously-synthesized ECM components; and (4) measure the binding of the ECM components to the substrates and determine whether this binding influences the ECM utilization by the cells. Data from this program will be used as a guide to manufacturing vastly improved collagen-coated microcarrier beads by incorporating fibronectin, laminin, and/or thrombospondin. Our distributors will use the improved performance to capture a sizeable market segment from a Swedish firm.