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The effects of microcarrier culture on recombinant CHO cells under biphasic hypothermic culture conditions

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Abstract

A Chinese hamster ovary (CHO) cell line, producing recombinant secreted human placental alkaline phosphatase (SEAP) was investigated under three different culture conditions (suspension cells, cells attached to Cytodex 3 and Cytopore 1 microcarriers) in a biphasic culture mode using a temperature shift to mild hypothermic conditions (33 °C) in a fed-batch bioreactor. The cell viability in both the suspension and the Cytodex 3 cultures was maintained for significantly longer periods under hypothermic conditions than in the single-temperature cultures, leading to higher integrated viable cell densities. For all culture conditions, the specific productivity of SEAP increased after the temperature reduction; the specific productivities of the microcarrier cultures increased approximately threefold while the specific productivity of the suspension culture increased nearly eightfold. The glucose and glutamine consumption rates and lactate and ammonia production rates were significantly lowered after the temperature reduction, as were the yields of lactate from glucose. However, the yield of ammonia from glutamine increased in response to the temperature shift.

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Acknowledgments

This work was supported in part by the National Science Foundation (BES-0075336). Cytodex 3 and Cytopore 1 microcarriers were generously provided by GE Healthcare.

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY, 12180, USA

    Jong Hyun Nam & Susan T. Sharfstein

  2. Département de Virologie, Institut Pasteur, 25 rue du Dr Roux, F-75015, Paris, France

    Myriam Ermonval

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  1. Jong Hyun Nam
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  2. Myriam Ermonval
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Correspondence to Susan T. Sharfstein.

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Nam, J.H., Ermonval, M. & Sharfstein, S.T. The effects of microcarrier culture on recombinant CHO cells under biphasic hypothermic culture conditions. Cytotechnology 59, 81–91 (2009). https://doi.org/10.1007/s10616-009-9196-x

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