Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation.

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation. Research Abstract Details 

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Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation. Abstract Text:

BACKGROUND: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. METHODOLOGY/PRINCIPAL FINDINGS: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. CONCLUSIONS: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum.

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Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: PLoS ONE

VOLUME: 3

Page Numbers: e2129

Journal Abbreviation: PLoS ONE

ISSN: 1932-6203

DAY: 7

MONTH: 05

YEAR: 2008

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation. Information

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LANGUAGE: eng

NlmUniqueID: 101285081

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Grant and Affiliation Information for Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation.

AFFILIATION: Department of Engineering Materials, University of Sheffield, Sheffield, United Kingdom.

Country: United States

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MEDLINETA: PLoS ONE

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