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International Conference on Mathematical Biology and

Annual Meeting of The Society for Mathematical Biology,

July 27-30, 2009

University of British Columbia, Vancouver

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Program

CTH7b
Edward Green
Ohio State University
Title Non-local models for the formation of hepatocyte - stellate cell aggregates
Abstract Liver cell aggregates may be grown in vitro by co-culturing hepatocytes with stellate cells. This method results in more rapid aggregation than hepatocyte-only culture, and appears to enhance cell viability and the expression of markers of liver-specific functions. We consider the early stages of aggregate formation, and present a new mathematical model to investigate two alternative hypotheses (based on evidence in the experimental literature) concerning how stellate cells promote aggregate formation. The first hypothesis is that each population produces a chemical signal which affects the other, and enhanced aggregation is due to chemotaxis. The second hypothesis asserts that direct physical contact between the different cell types is the dominant mechanism: the stellates extend long cellular processes which pull the hepatocytes into the aggregates). We formulate nonlocal (integro-partial differential) equations to describe the densities of cells, which are coupled to reaction-diffusion equations for the chemical concentrations. The behaviour of the model under each hypothesis is studied using a combination of linear stability analysis and numerical simulations. The results are compared with experimental observations and suggest that the hepatocyte-stellate attraction is strongest in practice. Based on this, we predict the optimal seeding ratio of hepatocytes to stellates for promoting rapid aggregate formation. We also suggest experiments which could be performed to discriminate between the two hypotheses.
LocationCHBE 102