Applied Cellular Physiology and Metabolic Engineering

Development of a mathematical model for evaluating the dynamics of normal and apoptotic Chinese hamster ovary cells

  1. Saeideh Naderi1,
  2. Mukesh Meshram1,
  3. Catherine Wei2,
  4. Brendan McConkey2,
  5. Brian Ingalls3,
  6. Hector Budman1,*,
  7. Jeno Scharer1

Article first published online: 25 MAY 2011

DOI: 10.1002/btpr.647

Issue

Biotechnology Progress

Biotechnology Progress

Volume 27, Issue 5, pages 1197–1205, September/October 2011

Additional Information

How to Cite

Naderi, S., Meshram, M., Wei, C., McConkey, B., Ingalls, B., Budman, H. and Scharer, J. (2011), Development of a mathematical model for evaluating the dynamics of normal and apoptotic Chinese hamster ovary cells. Biotechnol Progress, 27: 1197–1205. doi: 10.1002/btpr.647

Author Information

  1. 1

    Dept. of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada N2L 3G1

  2. 2

    Dept. of Biology, University of Waterloo, Waterloo, ON, Canada N2L 3G1

  3. 3

    Dept. of Applied Mathematics, University of Waterloo, Waterloo, ON, Canada N2L 3G1

*Dept. of Chemical Engineering, University of Waterloo, Waterloo, ON, Canada N2L 3G1

Publication History

  1. Issue published online: 10 OCT 2011
  2. Article first published online: 25 MAY 2011
  3. Accepted manuscript online: 2 MAY 2011 07:00AM EST
  4. Manuscript Revised: 24 JAN 2011
  5. Manuscript Received: 14 SEP 2010

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Keywords:

  • CHO;
  • metabolic flux analysis;
  • apoptosis;
  • mathematical modeling;
  • logistic equation

Abstract

A metabolic flux based methodology was developed for modeling the metabolism of a Chinese hamster ovary cell line. The elimination of insignificant fluxes resulted in a simplified metabolic network which was the basis for modeling the significant metabolites. Employing kinetic rate expressions for growing and non-growing subpopulations, a logistic model was developed for cell growth and dynamic models were formulated to describe culture composition and monoclonal antibody (MAb) secretion. The model was validated for a range of nutrient concentrations. Good agreement was obtained between model predictions and experimental data. The ultimate goal of this study is to establish a comprehensive dynamic model which may be used for model-based optimization of the cell culture for MAb production in both batch and fed-batch systems. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011

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