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

Self-prioritization and perceptual matching: The effects of temporal construal.

Recent research has revealed that self-referential processing enhances perceptual judgments - the so-called self-prioritization effect. The extent and origin of this effect remains unknown, however. Noting the multifaceted nature of the self, here we hypothesized that temporal influences on self-construal (i.e., past/future-self continuity) may serve as an important determinant of stimulus prioritization. Specifically, as representations of the self increase in abstraction as a function of temporal distance (i.e., distance from now), self-prioritization may only emerge when stimuli are associated with the current self. The results of three experiments supported this prediction. Self-relevance only enhanced performance in a standard perceptual-matching task when stimuli (i.e., geometric shapes) were connected with the current self; representations of the self in the future (Expts. 1 & 2) and past (Expt. 3) failed to facilitate decision making. To identify the processes underlying task performance, data were interrogated using a hierarchical drift diffusion model (HDDM) approach. Results of these analyses revealed that self-prioritization was underpinned by a stimulus bias (i.e., rate of information uptake). Collectively, these findings elucidate when and how self-relevance influences decisional processing