Monday, July 30, 2007 - 2:00 PM
S37
Modeling to accelerate mammalian cell bioprocessing: An evolving perspective from recombinant protein to stem cell systems
James M. Piret, Michael Smith Laboratories and Chemical & Biological Engineering, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada
Overly complex mathematical modeling of mammalian cell culture systems has been appropriately criticized over the past 20 years. For many in our field, this has left a generally negative impression of modeling. Though the overwhelming complexity of biology can make modeling efforts seem foolhardy, in fact there has been increased use of effective modeling. An evolving perspective on modeling will be illustrated with examples from a range of mammalian cell systems, from protein production, to gene and stem cell bioprocessing. Mechanistic modeling of physical phenomena in biological systems has been useful when developed for well defined and focused purposes such as the prediction of oxygen or protein transport limitations. Empirical modeling in the statistical design of experiments has also become widely used to identify the significant culture condition effects and interactions. Models guide bioprocess experimental design and interpretation, and provide a quantitative understanding of the critical factors even for highly complex biological systems. By sequentially adding critical mechanistic components, alternating between experimentation and simulation, mammalian cell modeling should further accelerate both the scientific understanding and the optimization of these dynamic biological engineering systems. The usefulness of such models is perhaps most impressive when it reveals coherent biological patterns in complex stem cell cultures consisting of mixed and differentiating populations. The contributions of mathematical modeling to biological research science should increasingly contribute to Systems Biology as well as cellular therapy research and development.