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Cell Attachment to Microcarriers Affects Growth, Metabolic Activity, and Culture Productivity in Bioreactor Culture

Authors

  • Jong Hyun Nam,

    1. Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180
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  • Myriam Ermonval,

    1. Différenciation cellulaire et prions, CNRS FRE 2937, Département de biologie cellulaire et Infection, Institut André Lwoff, Villejuif & Institut Pasteur, Paris, France
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  • Susan T. Sharfstein

    Corresponding author
    1. Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180
    • Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180. Fax: 518–276–4285.
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Abstract

It is not well understood how changes from suspension to microcarrier cultures affect cell growth, metabolism, and yield of recombinant proteins. To investigate the effects of culture conditions on cell characteristics, fed-batch bioreactor cultures were performed under different culture conditions (suspension cultures, cultures attached to Cytodex 3 and Cytopore 1 microcarriers) using two different Chinese hamster ovary cell lines producing either secreted human placental alkaline phosphatase (TR2–255) or tissue plasminogen activator (CHO 1–15–500). In controlled, agitated bioreactors, suspension cultures reached cell densities and product titers higher than those in microcarrier cultures, in contrast to the results in static flask cultures. Growth and metabolic activities showed similar trends in suspension and microcarrier culture regardless of cell line. However, the responses of the specific productivities to the different culture conditions differed significantly between the cell lines.

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