Document Detail

A mathematical model of liver cell aggregation in vitro.
MedLine Citation:
PMID:  19093155     Owner:  NLM     Status:  MEDLINE    
The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work.
J E F Green; S L Waters; K M Shakesheff; H M Byrne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-18
Journal Detail:
Title:  Bulletin of mathematical biology     Volume:  71     ISSN:  1522-9602     ISO Abbreviation:  Bull. Math. Biol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-07     Completed Date:  2009-06-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401404     Medline TA:  Bull Math Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  906-30     Citation Subset:  IM    
Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, University of Nottingham, Nottingham, NG7 2RD, UK.
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MeSH Terms
Cell Aggregation / physiology*
Extracellular Matrix / physiology
Hepatocytes / cytology*
Liver / cytology*
Models, Biological*
Tissue Engineering / methods
Grant Support
//Biotechnology and Biological Sciences Research Council

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