Modeling the Effect of Exogenous Calcium on Keratinocyte and HaCat Cell Proliferation and Differentiation Using an Agent-Based Computational Paradigm

Walker, Dawn; Sun, Tao; MacNeil, Sheila; Smallwood, R. H.

doi:10.1089/ten.2006.12.2301

Cited by 27 publications

(21 citation statements)

References 19 publications

(18 reference statements)

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“…Agent‐based models have been developed to analyse different treatment strategies with wound debridement and topical administration of growth factor . Many studies have used agent‐based models for a multiscale approach to wound healing …”

Section: Resultsmentioning

confidence: 99%

Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin

Uddin

Bayat

2017

Wound Repair Regeneration

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Tissue repair models are essential to explore the pathogenesis of wound healing and scar formation, identify new drug targets/biomarkers and to test new therapeutics. However, no animal model is an exact replicate of the clinical situation in man as in addition to differences in the healing of animal skin; the response to novel therapeutics can be variable when compared to human skin. The aim of this review is to evaluate currently available non-animal wound repair models in human skin, including: in silico, in vitro, ex vivo, and in vivo. The appropriate use of these models is extremely relevant to wound-healing research as it enables improved understanding of the basic mechanisms present in the wound healing cascade and aid in discovering better means to regulate them for enhanced healing or prevention of abnormal scarring. The advantage of in silico models is that they can be used as a first in virtue screening tool to predict the effect of a drug/stimulus on cells/tissues and help plan experimental research/clinical trial studies but remain theoretical until validated. In vitro models allow direct quantitative examination of an effect on specific cell types alone without incorporating other tissue-matrix components, which limits their utility. Ex vivo models enable immediate and short-term evaluation of a particular effect on cells and its surrounding tissue components compared with in vivo models that provide direct analysis of a stimulus in the living human subject before/during/after exposure to a stimulus. Despite clear advantages, there remains a lack of standardisation in design, evaluation and follow-up, for acute/chronic wounds and scars in all models. In conclusion, ideal models of wound healing research are desirable and should mimic not only the structure but also the cellular and molecular interactions, of wound types in human skin. Future models may also include organ/skin-on-a-chip with potential application in wound healing research.

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Section: Resultsmentioning

confidence: 99%

Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin

Uddin

Bayat

2017

Wound Repair Regeneration

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“…For a deeper introduction to the theoretical background of agent-based modeling see [16], [28] and for a more detailed description of the modeling tool FLAME, see previously published models e.g. [29], [30], [31], [32], [33]. The concept of this melanocyte-keratinocyte co-culture model is based on two earlier published models; a keratinocyte colony formation model [17] and a normal human keratinocyte – human dermal fibroblast co-culture model [18].…”

Section: Methodsmentioning

confidence: 99%

Understanding the Melanocyte Distribution in Human Epidermis: An Agent-Based Computational Model Approach

et al. 2012

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The strikingly even color of human skin is maintained by the uniform distribution of melanocytes among keratinocytes in the basal layer of the human epidermis. In this work, we investigated three possible hypotheses on the mechanism by which the melanocytes and keratinocytes organize themselves to generate this pattern. We let the melanocyte migration be aided by (1) negative chemotaxis due to a substance produced by the melanocytes themselves, or (2) positive chemotaxis due to a substance produced by keratinocytes lacking direct physical contact with a melanocyte, or (3) positive chemotaxis due to a substance produced by keratinocytes in a distance-to-melanocytes dependent manner. The three hypotheses were implemented in an agent-based computational model of cellular interactions in the basal layer of the human epidermis. We found that they generate mutually exclusive predictions that can be tested by existing experimental protocols. This model forms a basis for further understanding of the communication between melanocytes and other skin cells in skin homeostasis.

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“…In silico, the different peptides may be first assessed in mathematical agent‐based models. These models were previously shown to be useful for investigation of selected growth factors . Single‐cell in vitro models are the next step to characterize the effect of these peptides on viability, proliferation, motility and migration.…”

Section: Experimental Approachmentioning

confidence: 99%

Are melanocortin peptides future therapeutics for cutaneous wound healing?

Böhm

Luger

2019

Experimental Dermatology

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Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds α‐melanocyte‐stimulating hormone (α‐MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated α‐MSH peptides such as Lys‐Pro‐Val (KPV) as well as derivatives like Lys‐d‐Pro‐Thr (KdPT), the latter containing the amino acid sequence 193‐195 of interleukin‐1β, have been found to possess anti‐inflammatory effects but to lack the pigment‐inducing activity of α‐MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so‐far available data on melanocortin peptides and derivatives in wound healing.

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Modeling the Effect of Exogenous Calcium on Keratinocyte and HaCat Cell Proliferation and Differentiation Using an Agent-Based Computational Paradigm

Cited by 27 publications

References 19 publications

Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin

Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin

Understanding the Melanocyte Distribution in Human Epidermis: An Agent-Based Computational Model Approach

Are melanocortin peptides future therapeutics for cutaneous wound healing?

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