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Co-culture with fibroblasts in stiff 3D scaffolds increases CD54 and CD140a expression on macrophages.

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Τίτλος: Co-culture with fibroblasts in stiff 3D scaffolds increases CD54 and CD140a expression on macrophages.
Συγγραφείς: Ng JW; Department of Biochemistry & Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Centre for Cardiovascular Biology & Disease Research, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia., Rao ST; Holsworth Biomedical Research Centre, Department of Rural Clinical Sciences, La Trobe Rural Health School, La Trobe University, Bendigo, VIC, Australia., Field EH; Department of Biology, School of Science, RMIT University, Melbourne, VIC, Australia.; Aikenhead Centre for Medical Discovery, Fitzroy, VIC, Australia., Ritchie K; Department of Biochemistry & Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Centre for Cardiovascular Biology & Disease Research, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia., Wright MD; Department of Immunology & Pathology, Alfred Medical Research and Education Precinct, School of Translational Medicine, Monash University, Melbourne, VIC, Australia., Reynolds NP; Department of Biochemistry & Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Department of Biology, School of Science, RMIT University, Melbourne, VIC, Australia.; Aikenhead Centre for Medical Discovery, Fitzroy, VIC, Australia., Cutter SW; Department of Biochemistry & Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Centre for Cardiovascular Biology & Disease Research, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia., Binger KJ; Department of Biochemistry & Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.; Centre for Cardiovascular Biology & Disease Research, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, VIC, Australia.; Department of Biochemistry & Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
Πηγή: Frontiers in immunology [Front Immunol] 2026 Jun 03; Vol. 17, pp. 1771248. Date of Electronic Publication: 2026 Jun 03 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation]
Ιατρικοί όροι (MeSH): Macrophages*/metabolism , Macrophages*/immunology , Fibroblasts*/metabolism , Intercellular Adhesion Molecule-1*/metabolism , Intercellular Adhesion Molecule-1*/genetics , Tissue Scaffolds*, Animals ; Coculture Techniques ; Mice ; Cells, Cultured ; Cell Communication ; Cell Culture Techniques, Three Dimensional
Περίληψη: Vascular fibrosis is a major contributor to hypertension and cardiovascular disease and is caused by excessive extracellular matrix deposition and tissue stiffening. Macrophages and fibroblasts are key regulators of this process, yet most studies have relied on non-physiological two-dimensional (2D) in vitro culture systems, limiting their relevance. In this study, three-dimensional (3D) collagen-based scaffolds with tunable stiffnesses were developed to model the effect of fibrotic microenvironments on macrophage and fibroblast interactions. Bone-marrow derived macrophages (BMDMs) and mouse embryonic fibroblasts (MEFs) co-cultured in 3D maintained equivalent viability in scaffolds with a storage modulus of ~200 Pa and ~2000 Pa. Strikingly, during co-culture, macrophages, but not fibroblasts, exhibited a stiffness-dependent upregulation of CD54 (ICAM-1) and CD140a (PDGFRα), markers associated with inflammation and fibrosis. Confocal imaging revealed only occasional direct interaction between cell types, suggesting that the altered macrophage phenotype is driven by combined mechanical and soluble cues rather than increased physical interaction. Overall, these findings highlight the importance of dimensionality and stiffness in shaping macrophage-fibroblast crosstalk and provide a platform for dissecting mechanisms underlying vascular fibrosis.
(Copyright © 2026 Ng, Rao, Field, Ritchie, Wright, Reynolds, Cutter and Binger.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Contributed Indexing: Keywords: 3D culture; co-culture; macrophage activation; myofibroblast; vascular fibrosis
Substance Nomenclature: 126547-89-5 (Intercellular Adhesion Molecule-1)
Entry Date(s): Date Created: 20260619 Date Completed: 20260619 Latest Revision: 20260813
Update Code: 20260813
PubMed Central ID: PMC13272094
DOI: 10.3389/fimmu.2026.1771248
PMID: 42317321
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1664-3224
DOI:10.3389/fimmu.2026.1771248