title: Methods to study differences in cell mobility during skin wound healing in vitro.
abstract: Wound healing events which occur in humans are difficult to study in animals due to differences in skin physiology. Furthermore there are increasing restrictions in Europe for using animals for testing the therapeutic properties of new compounds. Therefore, in line with the 3Rs (reduction, refinement and replacement of test animals), a number of human in vitro models of different levels of complexity have been developed to investigate cell mobility during wound healing. Keratinocyte, melanocyte, fibroblast and endothelial cell mobility are described, since these are the residential cells which are responsible for restoring the main structural features of the skin. A monolayer scratch assay is used to study random fibroblast and endothelial cell migration in response to EGF and bFGF respectively and a chemotactic assay is used to study directional fibroblast migration towards CCL5. In order to study endothelial sprouting in response to bFGF or VEGF, which involves continuous degradation and resynthesis of a 3D matrix, a fibrin gel is used. Human physiologically relevant tissue-engineered skin models are used to investigate expansion of the stratified, differentiated epidermis (keratinocytes and melanocytes) over a fibroblast populated dermis and also to study migration and distribution of fibroblasts into the dermis. Together these skin models provide a platform for testing the mode of action of novel compounds for enhanced and scar free wound healing.
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hanneke N
authors.initials: HN
authors.lastname: Monsuur
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands; Department of Biochemistry, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, The Netherlands.
authors.forename: Mireille A
authors.initials: MA
authors.lastname: Boink
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands; A-Skin BV, Amsterdam, The Netherlands.
authors.forename: Ester M
authors.initials: EM
authors.lastname: Weijers
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Roffel
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: Breetveld
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Amit
authors.initials: A
authors.lastname: Gefen
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lenie J
authors.initials: LJ
authors.lastname: van den Broek
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands; Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, The Netherlands. Electronic address: s.gibbs@acta.nl.
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
mesh_terms: D001681:Biological Assay; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques / Q000379:methods*; D015603:Keratinocytes / Q000502:physiology; D008544:Melanocytes / Q000502:physiology; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D023822:Tissue Engineering; D014945:Wound Healing / Q000502:physiology*
keywords: 3Rs; In vitro; Migration; Skin; Wound healing