Speaker Simon Dornseifer (Universität des Saarlandes) will discuss how mathematical modelling of growth in Caco-2 cell cultures, widely used in the pharmaceutical industry, can help find the causes of population heterogeneity, which hinders experimental reproducibility.

An extra life sciences seminar about in silico modelling of Caco-2 cell cultures: influence of laboratory conditions and heterogeneity.

Caco-2 cells are a widely-used standard for in vitro permeation assays, simulating the absorption in human small intestine. Many experimentalists report variability in morphology and functional differentiation during culturing of genetically heterogeneous Caco-2 clones. Furthermore, recent studies suggest that cell lines like Caco-2 are highly depended on environmental factors.

Highly standardized set-ups and a characterization of the clones are demanded for reproducibility - but are expensive and by far not completed yet. In consequence, an in silico model of monolayer-forming cell populations was designed. It was parameterized and fitted to experimental Caco-2 cell line data. On the one hand, the tool simulates the influence of environmental perturbation such as subculturing, seeding density, and culture period. On the other hand, it accounts for heterogeneity within the cell population.

A large number of cell growth scenarios that are found in literature are simulated and the results are comparable with experimental observations. The simulations suggest fluctuating subpopulations depended on artificial selection pressure in laboratories and a sensitive dependency of these heterogeneous populations on environmental conditions.

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