An integrated systems biology approach to understanding the rules of keratinocyte colony formation (original) (raw)
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SCIENTIFIC ANALYSIS OF KERATINOCYTE COLONY FORMATION RULES
Agent based modelling provides a vital scientific understanding of differing systems and an additional framework with sophisticated innovative paradigms which allows the modelling of dynamic systems as well as natural systems. The specific objectives of this analyses and investigation were to use an existing Flame model, and use it for some virtual experiments which would enable the scientific analyses of keratinocyte colony formation, with the increasing of agents and alteration of key parameters such as cell cycle length and probability. Furthermore, one of the main objectives was also to determine the keratinocyte colony formation capacity, of keratinocyte in vitro and in virtuo models for normal human keratinocytes (NHK), this study will also explore the existing model to contrast the effectiveness of extracellular calcium level, analyse the cell seeding densities and see how cell culture is enhanced. We‟ll aim to analyse the negative and positive output of keratinocyte colony formation capacity, due to the changes in the cell cycle length of stem cells of keratinocyte colony formation and differentiation. With the deliberate purpose of broadening ones understanding and insight as to how changes to the latter and former do help human tissue healing in various demographics.
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Cultured primary human keratinocytes are frequently employed for studies of immunological and inflammatory responses; however, interpretation of experimental data may be complicated by donor to donor variability, the relatively short culture lifetime, and variations between passages. To standardize thestudies on keratinocytes, we investigated the use of HaCaT cells, a long-lived, spontaneously immortalized human keratinocyte line which is able to differentiate, as a suitable model to follow the release of inflammatory and repair mediators in response to TNFor IL-1. Different treatment conditions (presence or absence of serum) and differentiation stimuli (increase in cell density as a function of time in culture and elevation of extracellular calcium) were considered. ELISA and Multiplex measurement technologies were used to monitor the production of cytokines and chemokines. Taken together, the results highlight that Caconcentration in the medium, cell density, and presence of serum...
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Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.