ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Self-Assembled Human Skin Equivalents Model Macrophage Activation of Cutaneous Fibrogenesis in Systemic Sclerosis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Recent advances in immunocompetent human skin-on-chip models: Construction strategies and biomedical applications.Bioactive materials · 2026Review
- Macrophage programming in systemic sclerosis: Niches, networks, and translational horizons.Seminars in immunopathology · 2026Review
- Monocytes strongly induce (myo)fibroblast contraction in a 3D skin model to understand inflammation-fibrosis crosstalk.Scientific reports · 2026Article
- RUNX1 is expressed in a subpopulation of dermal fibroblasts and is associated with disease severity of systemic sclerosis.Annals of the rheumatic diseases · 2026Article
- Targeting Cathepsin B-mediated pyroptosis in fibroblasts alleviate ultraviolet-induced skin inflammation and injury.Cell communication and signaling : CCS · 2025Article
- An international perspective on the future of systemic sclerosis research.Nature reviews. Rheumatology · 2025Review
- Immunological control of skin development: from homeostasis to developmental pathologies.Frontiers in immunology · 2025Review
- Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening.Biofabrication · 2024Article
- Article
- Characterization of macrophages associated with human skin models exposed to UV radiation.Communications biology · 2024Article
- Macrophages in inflammatory skin diseases and skin tumors.Frontiers in immunology · 2024Review
- Engineering edgeless human skin with enhanced biomechanical properties.Science advances · 2023Article
- Regulatory Mechanism of M1/M2 Macrophage Polarization in the Development of Autoimmune Diseases.Mediators of inflammation · 2023Review
- Contribution of keratinocytes to dermal fibrosis.Current opinion in rheumatology · 2022Review
- The Mechanism and Regulation of the NLRP3 Inflammasome during Fibrosis.Biomolecules · 2022Review
- Advancing skin model development: A focus on a self-assembled, induced pluripotent stem cell-derived, xeno-free approach.Journal of tissue engineeringArticle
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveThe development of precision therapeutics for systemic sclerosis (SSc) has been hindered by the lack of models that accurately mimic the disease in vitro. This study was undertaken to design and test a self-assembled skin equivalent (saSE) system that recapitulates the cross-talk between macrophages and fibroblasts in cutaneous fibrosis.
methodsSSc-derived dermal fibroblasts (SScDFs) and normal dermal fibroblasts (NDFs) were cultured with CD14+ monocytes from SSc patients or healthy controls to allow de novo stroma formation. Monocyte donor-matched plasma was introduced at week 3 prior to seeding keratinocytes to produce saSE with a stratified epithelium. Tissue was characterized by immunohistochemical staining, atomic force microscopy, enzyme-linked immunosorbent assay, and quantitative reverse transcriptase-polymerase chain reaction.
resultsStroma synthesized de novo from NDFs and SScDFs supported a fully stratified epithelium to form saSE. A thicker and stiffer dermis was generated by saSE with SScDFs, and more interleukin-6 and transforming growth factor β (TGFβ) was secreted by saSE with SScDFs compared to saSE with NDFs, regardless of the inclusion of monocytes. Tissue with SSc monocytes and plasma had amplified dermal thickness and stiffness relative to control tissue. Viable CD163+ macrophages were found within the stroma of saSE 5 weeks after seeding. Additionally, SSc saSE contained greater numbers of CD163+ and CD206+ macrophages compared to control saSE. TGFβ blockade inhibited stromal stiffness to a greater extent in SSc saSE compared to control saSE.
conclusionThese data suggest reciprocal activation between macrophages and fibroblasts that increases tissue thickness and stiffness, which is dependent in part on TGFβ activation. The saSE system may serve as a platform for preclinical therapeutic testing and for molecular characterization of SSc skin pathology through recapitulation of the interactions between macrophages and fibroblasts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.