A CELLULAR-AUTOMATON MODEL FOR MICROCARRIER CULTURES

In order to achieve high cell densities anchorage-dependent cells are commonly cultured on microcarriers, where spatial restrictions to cell growth complicates the determination of the growth kinetics. To desig n and operate large-scale bioreactors for microcarrier cultures, the e ffect of this spatial restriction to growth, referred to as contact in hibition, must be decoupled from the growth kinetics. In this article, a cellular automaton approach is recommended to model the growth of a nchorage-dependent cells on microcarriers. The proposed model is simpl e to apply yet provides an accurate representation of contact-inhibite d cell growth on microcarriers. The distribution of the number of neig hboring cells per cell, microcarrier surface areas, and inoculation de nsities are taken into account with this model. When compared with exp erimental data for Vero and MRC-5 microcarrier cultures, the cellular automaton predictions were very good. Furthermore, the model can be us ed to generate contact-inhibition growth curves to decouple the effect of contact inhibition from growth kinetics. With this information, th e accurate determination of kinetic parameters, such as nutrient uptak e rates, and the effects of other environmental factors, such as toxin levels, may be determined. (C) 1994 John Wiley & Sons, Inc.