Eyelid and Sternum Fibroblasts Differ in Their Contraction Potential and Responses to Inflammatory Cytokines

Abstract

Background:Adverse skin scarring varies by anatomical site with, for example, presternal skin showing a greater hypertrophic response when compared with eyelid; such differences have traditionally been attributed to regional variations in skin tension, thickness, and Langer’s lines. Fibroblasts are the main cell implicated in fibrosis, and they too are known to show anatomical variation in their expression, differentiation, and intercellular interactions. We, therefore, investigated whether intrinsic differences in skin fibroblasts derived from separate locations might contribute to the observed discrepancies in clinical scarring.Methods:Primary in vitro cultures were established using matched eyelid and presternal skin from 3 healthy donors undergoing blepharoplasty surgery. We used an in vitro collagen gel model of fibroblast-mediated tissue contraction to compare the properties of the dermal fibroblasts from each site. Cell contractile force and matrix stiffness were assessed in 3-dimensional tissue constructs using an automated high-throughput device.Results:Dermal fibroblasts isolated from eyelid and sternum differ both in their ability to contract a gel matrix and in their response to cytokine stimulation; despite having lower intrinsic contractile force (P < 0.01) and resting stiffness (P < 0.02), the presternal cells were more contractile (P < 0.001) following stimulation with serum, or inflammatory cytokines transforming growth factor-β (P < 0.01) and interleukin-1β (P < 0.05).Conclusions:The propensity to cutaneous scarring may, at least in part, result from intrinsic differences in the local fibroblasts’ ability to contract and their sensitivity to inflammatory cytokines. Improved understanding of the underlying molecular pathways should prove useful in identifying new therapeutic targets for altering surgical and other scarring.

Assessment of solid microneedle rollers to enhance transmembrane delivery of doxycycline and inhibition of MMP activity

“…The biopsy was mechanically dispersed, outgrown from the explant and established as a primary in vitro culture (Li et al, 2015). Monolayer cultures of fibroblasts were grown in T75 cm 2 vented flasks in Â1 DMEM (Sigma-Aldrich, Poole, UK) supplemented with 10% (v/v) FBS (Gibco, Paisley, UK), 1% (v/v) L-glutamine (Sigma-Aldrich) and 1% (v/v) penicillin-streptomycin-amphotericin B (Sigma-Aldrich).…”

Macrophages promote a profibrotic phenotype in orbital fibroblasts through increased hyaluronic acid production and cell contractility

“…However, while both control and GO orbital fibroblasts express αSMA, we found that macrophage-mediated stimulation of fibroblast contractility was not linked to αSMA expression; rather, macrophages stimulated actin dynamics in fibroblasts, with increased protrusive activity and actin polymerization. We have shown previously that such dynamic protrusive activity in 3D gels is sufficient to generate contractile force in primary human fibroblasts, and may represent an alternate pathway to the fibrotic phenotype 21,54–56 . Consistent with this, macrophage-mediated contractility in orbital fibroblasts was not prevented by blocking TGF-β signalling, the classical upstream pathway mediating the acquisition of the myofibroblast phenotype 57 .…”

A Comparative Assessment of Scars Resulting From Skin Grafts in Facial Defects

“…18,19 Myofibroblasts differentiate from fibroblasts in dermis and have intrinsic contractile properties imbued by alpha-actin filament bundles, though notably, the degree of fibroblast differentiation depends on wound location. 20 Because degree of fibroblast to myofibroblast differentiation and contractile forces are low in the periorbital area 21 and because MatriDerm suppress this fibroblast differentiation, 22 it is explainable that the use of STSG with a dermal substitute might be expected to produce comparable or better aesthetic results than FTSG in periorbital area.…”