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

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

Caribbean Plate Relative Motions

Any reconstruction of the geological history of the Central America land bridge is dependent on conjectural motions of several lithospheric plates. The most important aspect of a timing sequence for a link between the North and South America land masses is apparently the creation of the Caribbean Plate. The geological record, however, which details a tectonic evolution of the Caribbean Plate and its margins is so enigmatic that many critical questions remain unresolved, and every developed model is couched in some incompatibilities

Mesozoic and Cenozoic Plate Evolution of the Caribbean Region

The reconstruction of Caribbean plate history is an uncertain task, but a task that has intrigued generations of geologists. Each worker has turned to the task of historical interpretation influenced by a particular set of experiences or a special approach, and the results have been accordingly varied. A complete history of interpretations would form the subject of a fascinating chapter in the history of geological philosophy, but such is not the purpose of this chapter. Instead, I will dwell on a set of data that call for what I believe to be a relatively conservative view of Cretaceous and Tertiary plate history. My own interpretation is based heavily on my own or my students’ field experiences in the northeastern West Indies, Guatemala, Belize, and Venezuela, as well as extensive field excursions in Hispaniola, Jamaica, the Lesser Antilles, Central America, and the Dutch Antilles. I am further heavily influenced by the results of the Deep Sea Drilling Project (DSDP), Leg 15, which produced information of fundamental interest in the Venezuelan and Colombian Basins, and by several dissertations of the Princeton University group in northern Venezuela