ArticlePloS one2009
Exploring hypotheses of the actions of TGF-beta1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
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- Free and Interfacial Boundaries in Individual-Based Models of Multicellular Biological systems.Bulletin of mathematical biology · 2023Article
- Modelling the Effect of Matrix Metalloproteinases in Dermal Wound Healing.Bulletin of mathematical biology · 2023Article
- Multiscale modelling of desquamation in the interfollicular epidermis.PLoS computational biology · 2022Article
- TopicalWorld journal of plastic surgery · 2022Article
- Agent-Based Modeling of Complex Molecular Systems.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Mathematical Model Predicts that Acceleration of Diabetic Wound Healing is Dependent on Spatial Distribution of VEGF-A mRNA (AZD8601).Cellular and molecular bioengineering · 2021Article
- A computational model of the epidermis with the deformable dermis and its application to skin diseases.Scientific reports · 2021Article
- The greater inflammatory pathway-high clinical potential by innovative predictive, preventive, and personalized medical approach.The EPMA journal · 2020Review
- Uncertainty quantification on a spatial Markov-chain model for the progression of skin cancer.Journal of mathematical biology · 2020Article
- Computational model of wound healing: EGF secreted by fibroblasts promotes delayed re-epithelialization of epithelial keratinocytes.Integrative biology : quantitative biosciences from nano to macro · 2018Article
- Cell studio: A platform for interactive, 3D graphical simulation of immunological processes.APL bioengineering · 2018Article
- Structural Characterization and Statistical-Mechanical Model of Epidermal Patterns.Biophysical journal · 2016Article
- Mathematical Models for Immunology: Current State of the Art and Future Research Directions.Bulletin of mathematical biology · 2016Review
- Augmenting Surgery via Multi-scale Modeling and Translational Systems Biology in the Era of Precision Medicine: A Multidisciplinary Perspective.Annals of biomedical engineering · 2016Review
- FOXO1 differentially regulates both normal and diabetic wound healing.The Journal of cell biology · 2015Article
- Strategies for efficient numerical implementation of hybrid multi-scale agent-based models to describe biological systems.Cellular and molecular bioengineering · 2015Article
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units (keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged (by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing.
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