ArticleFrontiers in immunology2023
A novel 3D spheroid model of rheumatoid arthritis synovial tissue incorporating fibroblasts, endothelial cells, and macrophages.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Arthritis models for studying chikungunya virus joint inflammation.Communications biology · 2026Review
- Immune-stromal interactions at the crossroads of tissue injury, repair, and tumor progression.Med (New York, N.Y.) · 2026Review
- Engineering autoimmune disease models using organoids: Harnessing microenvironmental engineering for precision medicine and immunological recapitulation.Bioengineering & translational medicine · 2026Review
- Murine and Humanized Mouse Models in Autoimmune Disease Research and Therapeutics Development.Biology · 2026Review
- Targeting inflammatory and angiogenic responses by small-molecule kinase inhibitors in a 3D macrophage-containing spheroid model of rheumatoid arthritis synovial tissue.Arthritis research & therapy · 2026Article
- Scalable synovial fibroblast sources enable reproducible basal synovial organoid formation: an in vitro platform study.Rheumatology international · 2026Article
- AI-integrated microfluidics for drug screening: From single cell to organ-on-a-chip.Acta pharmaceutica Sinica. B · 2026Review
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- FGF/FGFR signaling at the immune-stromal interface in autoimmune rheumatic diseases: from tissue remodeling to translational opportunities.Frontiers in immunology · 2026Review
- Pirfenidone Attenuates Fibrosis and Neovascularization in 3D Spheroid-Laden Hydrogel Culture.Journal of tissue engineering and regenerative medicine · 2026Article
- 3D Bioprinting Strategies in Autoimmune Disease Models.International journal of molecular sciences · 2025Review
- Synovium-On-A-Chip: Simulating the Microenvironment of the Rheumatoid Arthritis Synovium via Multicell Interactions to Target Fibroblast-Like Synoviocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Can alternatives to animal testing yield useful information regarding biological mechanisms and drug discovery?Journal of orthopaedic translation · 2025Review
- An Animal-Free Patient-Derived Tissue-Mimetic Biochip Model of the Human Synovial Membrane for Human-Relevant Osteoarthritis Research.Advanced healthcare materials · 2025Article
- Synovial organoids: From fundamental construction to groundbreaking applications in arthritic disorders.Journal of orthopaedic translation · 2025Review
- Synovial Organoids and Cell Culture Models: An Ideal Platform for Exploring Traditional Chinese Medicine in Rheumatoid Arthritis.ACS omega · 2025Review
- Immune Organoids: A Review of Their Applications in Cancer and Autoimmune Disease Immunotherapy.Current issues in molecular biology · 2025Review
- Pharmacological Inhibition of the PI3K/AKT/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical).Pharmaceuticals (Basel, Switzerland) · 2025Review
- Constructing a 3D co-cultureMaterials today. Bio · 2025Article
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Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Rheumatoid Arthritis (RA) is a progressive and systemic autoimmune disorder associated with chronic and destructive joint inflammation. The hallmarks of joint synovial inflammation are cellular proliferation, extensive neoangiogenesis and infiltration of immune cells, including macrophages. Methods: Spheroids were generated by culturing RA fibroblast-like-synoviocytes (RAFLS), human umbilical vein endothelial cells (ECs) and monocyte-derived macrophages in a collagen-based 3D scaffold. The spheroids were cultured in the presence or absence of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (bFGF) or RA synovial fluid (SF). Spheroid expansion and cell migration were quantified for all conditions using confocal microscopy and digital image analysis. Results: A novel approach using machine learning was developed to quantify spheroid outgrowth and used to reexamine the existing spheroid-based model of RA synovial angiogenesis consisting of ECs and RAFLS. A 2-fold increase in the spheroid outgrowth ratio was demonstrated upon VEGF/bFGF stimulation ( Conclusion: We present a novel spheroid based model consisting of RAFLS, ECs and macrophages that reflects the RA synovial tissue microenvironment. This model may be used to dissect the role of specific cell types in inflammatory responses in RA, to study specific signaling pathways involved in the disease pathogenesis and examine the effects of novel diagnostic (molecular imaging) and therapeutic compounds, including small molecule inhibitors and biologics.
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