Hussey, G. S., Dziki, J. L. & Badylak, S. F. Extracellular matrix-based materials for regenerative medicine. Nat. Rev. Mater. 3, 159–173 (2018).
Google Scholar
Badylak, S. F., Freytes, D. O. & Gilbert, T. W. Extracellular matrix as a biological scaffold material: structure and function. Acta Biomater. 5, 1–13 (2009).
Google Scholar
Bissell, M. J., Hall, H. G. & Parry, G. How does the extracellular matrix direct gene expression? J. Theor. Biol. 99, 31–68 (1982).
Google Scholar
Brown, B. N. et al. Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater. 8, 978–987 (2012).
Google Scholar
Dziki, J. L. et al. Solubilized extracellular matrix bioscaffolds derived from diverse source tissues differentially influence macrophage phenotype. J. Biomed. Mater. Res. A 105, 138–147 (2017).
Google Scholar
Petrosyan, A. et al. A step towards clinical application of acellular matrix: a clue from macrophage polarization. Matrix Biol. 57–58, 334–346 (2017).
Google Scholar
Huleihel, L. et al. Matrix-bound nanovesicles recapitulate extracellular matrix effects on macrophage phenotype. Tissue Eng. Part A 23, 1283–1294 (2017).
Google Scholar
Keane, T. J. et al. Restoring mucosal barrier function and modifying macrophage phenotype with an extracellular matrix hydrogel: potential therapy for ulcerative colitis. J. Crohns Colitis 11, 360–368 (2017).
Google Scholar
Huleihel, L. et al. Matrix-bound nanovesicles within ECM bioscaffolds. Sci. Adv. 2, e1600502 (2016).
Google Scholar
Huleihel, L. et al. Macrophage phenotype in response to ECM bioscaffolds. Semin. Immunol. 29, 2–13 (2017).
Google Scholar
Sicari, B. M. et al. The promotion of a constructive macrophage phenotype by solubilized extracellular matrix. Biomaterials 35, 8605–8612 (2014).
Google Scholar
Brown, B. N., Valentin, J. E., Stewart-Akers, A. M., McCabe, G. P. & Badylak, S. F. Macrophage phenotype and remodeling outcomes in response to biologic scaffolds with and without a cellular component. Biomaterials 30, 1482–1491 (2009).
Google Scholar
Londono, R. et al. The effect of cell debris within biologic scaffolds upon the macrophage response. J. Biomed. Mater. Res. A 105, 2109–2118 (2017).
Google Scholar
Naranjo, J. D. et al. Esophageal extracellular matrix hydrogel mitigates metaplastic change in a dog model of Barrett’s esophagus. Sci. Adv. 6, eaba4526 (2020).
Google Scholar
Saldin, L. T. et al. The effect of normal, metaplastic, and neoplastic esophageal extracellular matrix upon macrophage activation. J. Immunol. Regen. Med 13, 100037 (2021).
Google Scholar
Meng, F. W., Slivka, P. F., Dearth, C. L. & Badylak, S. F. Solubilized extracellular matrix from brain and urinary bladder elicits distinct functional and phenotypic responses in macrophages. Biomaterials 46, 131–140 (2015).
Google Scholar
Ploeger, D. T. A., van Putten, S. M., Koerts, J. A., van Luyn, M. J. A. & Harmsen, M. C. Human macrophages primed with angiogenic factors show dynamic plasticity, irrespective of extracellular matrix components. Immunobiology 217, 299–306 (2012).
Google Scholar
Londono, R. & Badylak, S. F. Biologic scaffolds for regenerative medicine: mechanisms of in vivo remodeling. Ann. Biomed. Eng. 43, 577–592 (2015).
Google Scholar
Badylak, S. F. The extracellular matrix as a biologic scaffold material. Biomaterials 28, 3587–3593 (2007).
Google Scholar
Hussey, G. S. et al. Lipidomics and RNA sequencing reveal a novel subpopulation of nanovesicle within extracellular matrix biomaterials. Sci. Adv. 6, eaay4361 (2020).
Google Scholar
van der Merwe, Y., Faust, A. E. & Steketee, M. B. Matrix bound vesicles and miRNA cargoes are bioactive factors within extracellular matrix bioscaffolds. Neural Regen. Res. 12, 1597–1599 (2017).
Google Scholar
Zhu, W. et al. Anti-citrullinated protein antibodies induce macrophage subset disequilibrium in RA patients. Inflammation 38, 2067–2075 (2015).
Google Scholar
Fukui, S. et al. M1 and M2 monocytes in rheumatoid arthritis: a contribution of imbalance of M1/M2 monocytes to osteoclastogenesis. Front. Immunol. 8, 1958 (2017).
Google Scholar
Kennedy, A., Fearon, U., Veale, D. J. & Godson, C. Macrophages in synovial inflammation. Front. Immunol. 2, 52 (2011).
Google Scholar
Feldmann, M., Brennan, F. M. & Maini, R. N. Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14, 397–440 (1996).
Google Scholar
Iwamoto, T., Okamoto, H., Toyama, Y. & Momohara, S. Molecular aspects of rheumatoid arthritis: chemokines in the joints of patients. FEBS J. 275, 4448–4455 (2008).
Google Scholar
Smolen, J. S. et al. Rheumatoid arthritis. Nat. Rev. Dis. Prim. 4, 18001 (2018).
Google Scholar
Feldmann, M., Brennan, F. M. & Maini, R. N. Rheumatoid arthritis. Cell 85, 307–310 (1996).
Google Scholar
Iguchi, T., Kurosaka, M. & Ziff, M. Electron microscopic study of HLA-DR and monocyte/macrophage staining cells in the rheumatoid synovial membrane. Arthritis Rheum. 29, 600–613 (1986).
Google Scholar
Siouti, E. & Andreakos, E. The many facets of macrophages in rheumatoid arthritis. Biochem. Pharmacol. 165, 152–169 (2019).
Google Scholar
Kinne, R. W., Bräuer, R., Stuhlmüller, B., Palombo-Kinne, E. & Burmester, G. R. Macrophages in rheumatoid arthritis. Arthritis Res. 2, 189–202 (2000).
Google Scholar
Cauli, A., Yanni, G. & Panayi, G. S. Interleukin-1, interleukin-1 receptor antagonist and macrophage populations in rheumatoid arthritis synovial membrane. Br. J. Rheumatol. 36, 935–940 (1997).
Google Scholar
Ridley, M. G., Kingsley, G., Pitzalis, C. & Panayi, G. S. Monocyte activation in rheumatoid arthritis: evidence for in situ activation and differentiation in joints. Br. J. Rheumatol. 29, 84–88 (1990).
Google Scholar
Sun, W. et al. Targeting notch-activated M1 macrophages attenuates joint tissue damage in a mouse model of inflammatory arthritis. J. Bone Miner. Res. 32, 1469–1480 (2017).
Google Scholar
Kinne, R. W., Stuhlmüller, B. & Burmester, G.-R. Cells of the synovium in rheumatoid arthritis. Macrophages. Arthritis Res. Ther. 9, 224 (2007).
Google Scholar
Alivernini, S. et al. Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis. Nat. Med. 26, 1295–1306 (2020).
Google Scholar
Kuan, W. P. et al. CXCL 9 and CXCL 10 as sensitive markers of disease activity in patients with rheumatoid arthritis. J. Rheumatol. 37, 257–264 (2010).
Google Scholar
Lee, J.-H. et al. Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: relevance for arthritis. Arthritis Res. Ther. 19, 163 (2017).
Google Scholar
Katschke, K. J. et al. Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis. Arthritis Rheum. 44, 1022–1032 (2001).
Google Scholar
Szekanecz, Z., Vegvari, A., Szabo, Z. & Koch, A. E. Chemokines and chemokine receptors in arthritis. Front. Biosci. (Sch. Ed.) 2, 153–167 (2010).
Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017).
Google Scholar
Brown, B. N., Ratner, B. D., Goodman, S. B., Amar, S. & Badylak, S. F. Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 33, 3792–3802 (2012).
Google Scholar
Badylak, S. F. Extracellular matrix and the immune system: friends or foes. Nat. Rev. Urol. 16, 389–390 (2019).
Google Scholar
Badylak, S. F. et al. Biologic scaffolds for constructive tissue remodeling. Biomaterials 32, 316–319 (2011).
Google Scholar
Badylak, S. F., Valentin, J. E., Ravindra, A. K., McCabe, G. P. & Stewart-Akers, A. M. Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng. Part A 14, 1835–1842 (2008).
Google Scholar
Agrawal, V. et al. Epimorphic regeneration approach to tissue replacement in adult mammals. Proc. Natl Acad. Sci. USA 107, 3351–3355 (2010).
Google Scholar
Allman, A. J. et al. Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response. Transplantation 71, 1631–1640 (2001).
Google Scholar
Beattie, A. J., Gilbert, T. W., Guyot, J. P., Yates, A. J. & Badylak, S. F. Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. Tissue Eng. Part A 15, 1119–1125 (2009).
Google Scholar
Allman, A. J., McPherson, T. B., Merrill, L. C., Badylak, S. F. & Metzger, D. W. The Th2-restricted immune response to xenogeneic small intestinal submucosa does not influence systemic protective immunity to viral and bacterial pathogens. Tissue Eng. 8, 53–62 (2002).
Google Scholar
Dziki, J. L., Huleihel, L., Scarritt, M. E. & Badylak, S. F. Extracellular matrix bioscaffolds as immunomodulatory biomaterials. Tissue Eng. Part A 23, 1152–1159 (2017).
Google Scholar
Badylak, S. F., Dziki, J. L., Sicari, B. M., Ambrosio, F. & Boninger, M. L. Mechanisms by which acellular biologic scaffolds promote functional skeletal muscle restoration. Biomaterials 103, 128–136 (2016).
Google Scholar
van der Merwe, Y. et al. Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function. Sci. Rep. 9, 3482 (2019).
Google Scholar
Sicari, B. M. et al. An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci. Transl. Med. 6, 234ra58 (2014).
Google Scholar
Sicari, B. M. et al. A murine model of volumetric muscle loss and a regenerative medicine approach for tissue replacement. Tissue Eng. Part A 18, 1941–1948 (2012).
Google Scholar
Dziki, J. et al. An acellular biologic scaffold treatment for volumetric muscle loss: results of a 13-patient cohort study. npj Regen. Med. 1, 16008 (2016).
Google Scholar
Turner, N. J., Badylak, J. S., Weber, D. J. & Badylak, S. F. Biologic scaffold remodeling in a dog model of complex musculoskeletal injury. J. Surg. Res. 176, 490–502 (2012).
Google Scholar
Friedman, B. & Cronstein, B. Methotrexate mechanism in treatment of rheumatoid arthritis. Jt. Bone Spine 86, 301–307 (2019).
Google Scholar
Ahuja, V., Miller, S. E. & Howell, D. N. Identification of two subpopulations of rat monocytes expressing disparate molecular forms and quantities of CD43. Cell Immunol. 163, 59–69 (1995).
Google Scholar
Thomas, G., Tacke, R., Hedrick, C. C. & Hanna, R. N. Nonclassical patrolling monocyte function in the vasculature. Arterioscler. Thromb. Vasc. Biol. 35, 1306–1316 (2015).
Google Scholar
Barnett-Vanes, A., Sharrock, A., Birrell, M. A. & Rankin, S. A single 9-colour flow cytometric method to characterise major leukocyte populations in the rat: validation in a model of LPS-induced pulmonary inflammation. PLoS ONE 11, e0142520 (2016).
Google Scholar
Misharin, A. V. et al. Nonclassical Ly6C(−) monocytes drive the development of inflammatory arthritis in mice. Cell Rep. 9, 591–604 (2014).
Google Scholar
Vingsbo, C. et al. Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am. J. Pathol. 149, 1675–1683 (1996).
Google Scholar
Hoffmann, M. H. et al. The rheumatoid arthritis-associated autoantigen hnRNP-A2 (RA33) is a major stimulator of autoimmunity in rats with pristane-induced arthritis. J. Immunol. 179, 7568–7576 (2007).
Google Scholar
Tuncel, J. et al. Animal models of rheumatoid arthritis (I): pristane-induced arthritis in the rat. PLoS ONE 11, e0155936 (2016).
Google Scholar
Huber, L. C. et al. Synovial fibroblasts: key players in rheumatoid arthritis. Rheumatology 45, 669–675 (2006).
Google Scholar
Yang, C. & Robbins, P. D. Immunosuppressive exosomes: a new approach for treating arthritis. Int. J. Rheumatol. 2012, 573528 (2012).
Google Scholar
Kim, S.-H. et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J. Immunol. 174, 6440–6448 (2005).
Google Scholar
Ruffner, M. A. et al. B7-1/2, but not PD-L1/2 molecules, are required on IL-10-treated tolerogenic DC and DC-derived exosomes for in vivo function. Eur. J. Immunol. 39, 3084–3090 (2009).
Google Scholar
Kim, S. H., Bianco, N. R., Shufesky, W. J., Morelli, A. E. & Robbins, P. D. Effective treatment of inflammatory disease models with exosomes derived from dendritic cells genetically modified to express IL-4. J. Immunol. 179, 2242–2249 (2007).
Google Scholar
Kim, S. H. et al. Exosomes derived from genetically modified DC expressing FasL are anti-inflammatory and immunosuppressive. Mol. Ther. 13, 289–300 (2006).
Google Scholar
Bianco, N. R., Kim, S. H., Ruffner, M. A. & Robbins, P. D. Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase-positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis Rheum. 60, 380–389 (2009).
Google Scholar
Kim, S. H., Bianco, N. R., Shufesky, W. J., Morelli, A. E. & Robbins, P. D. MHC class II+ exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J. Immunol. 179, 2235–2241 (2007).
Google Scholar
Quijano, L. M. et al. Matrix-bound nanovesicles: the effects of isolation method upon yield, purity, and function. Tissue Eng. Part C 26, 528–540 (2020).
Google Scholar
Schulze-Koops, H. & Kalden, J. R. The balance of Th1/Th2 cytokines in rheumatoid arthritis. Best. Pract. Res. Clin. Rheumatol. 15, 677–691 (2001).
Google Scholar
Roberts, C. A., Dickinson, A. K. & Taams, L. S. The interplay between monocytes/macrophages and CD4(+) T cell subsets in rheumatoid arthritis. Front. Immunol. 6, 571 (2015).
Google Scholar
Walter, G. J. et al. Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4+CD45ro+CD25+CD127(low) regulatory T cells. Arthritis Rheum. 65, 627–638 (2013).
Google Scholar
Evans, H. G. et al. In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proc. Natl Acad. Sci. USA 106, 6232–6237 (2009).
Google Scholar
van Amelsfort, J. M. R. et al. Proinflammatory mediator-induced reversal of CD4+,CD25+ regulatory T cell-mediated suppression in rheumatoid arthritis. Arthritis Rheum. 56, 732–742 (2007).
Google Scholar
Köller, M. et al. Expression of adhesion molecules on synovial fluid and peripheral blood monocytes in patients with inflammatory joint disease and osteoarthritis. Ann. Rheum. Dis. 58, 709–712 (1999).
Google Scholar
Müller-Ladner, U., Ospelt, C., Gay, S., Distler, O. & Pap, T. Cells of the synovium in rheumatoid arthritis. Synovial fibroblasts. Arthritis Res. Ther. 9, 223 (2007).
Google Scholar
Pretzel, D., Pohlers, D., Weinert, S. & Kinne, R. W. In vitro model for the analysis of synovial fibroblast-mediated degradation of intact cartilage. Arthritis Res. Ther. 11, R25 (2009).
Google Scholar
Danks, L. et al. RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. Ann. Rheum. Dis. 75, 1187–1195 (2016).
Google Scholar
Kramer, I., Wibulswas, A., Croft, D. & Genot, E. Rheumatoid arthritis: targeting the proliferative fibroblasts. Prog. Cell Cycle Res. 5, 59–70 (2003).
Google Scholar
Pap, T., Müller-Ladner, U., Gay, R. E. & Gay, S. Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. Arthritis Res. 2, 361–367 (2000).
Google Scholar
Odobasic, D. et al. Formyl peptide receptor activation inhibits the expansion of effector T cells and synovial fibroblasts and attenuates joint injury in models of rheumatoid arthritis. Int. Immunopharmacol. 61, 140–149 (2018).
Google Scholar
Pap, T., Cinski, A., Baier, A., Gay, S. & Meinecke, I. Modulation of pathways regulating both the invasiveness and apoptosis in rheumatoid arthritis synovial fibroblasts. Jt. Bone Spine: Rev. Rhum. 70, 477–479 (2003).
Andreas, K. et al. Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study. Arthritis Res. Ther. 10, R9 (2008).
Google Scholar
Korb-Pap, A. et al. Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis. Ann. Rheum. Dis. 71, 1004–1011 (2012).
Google Scholar
Meyer, L.-H., Franssen, L. & Pap, T. The role of mesenchymal cells in the pathophysiology of inflammatory arthritis. Best. Pract. Res. Clin. Rheumatol. 20, 969–981 (2006).
Google Scholar
Donlin, L. T., Jayatilleke, A., Giannopoulou, E. G., Kalliolias, G. D. & Ivashkiv, L. B. Modulation of TNF-induced macrophage polarization by synovial fibroblasts. J. Immunol. 193, 2373–2383 (2014).
Google Scholar
Rengel, Y., Ospelt, C. & Gay, S. Proteinases in the joint: clinical relevance of proteinases in joint destruction. Arthritis Res. Ther. 9, 221 (2007).
Google Scholar
Burrage, P. S., Mix, K. S. & Brinckerhoff, C. E. Matrix metalloproteinases: role in arthritis. Front. Biosci. 11, 529–543 (2006).
Google Scholar
Page-McCaw, A., Ewald, A. J. & Werb, Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat. Rev. Mol. Cell Biol. 8, 221–233 (2007).
Google Scholar
McInnes, I. B. & Schett, G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol. 7, 429–442 (2007).
Google Scholar
Catterall, J. B. et al. Synergistic induction of matrix metalloproteinase 1 by interleukin-1alpha and oncostatin M in human chondrocytes involves signal transducer and activator of transcription and activator protein 1 transcription factors via a novel mechanism. Arthritis Rheum. 44, 2296–2310 (2001).
Google Scholar
Eberhardt, W., Huwiler, A., Beck, K. F., Walpen, S. & Pfeilschifter, J. Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J. Immunol. 165, 5788–5797 (2000).
Google Scholar
Wei, S., Kitaura, H., Zhou, P., Ross, F. P. & Teitelbaum, S. L. IL-1 mediates TNF-induced osteoclastogenesis. J. Clin. Investig. 115, 282–290 (2005).
Google Scholar
Dayer, J.-M. & Bresnihan, B. Targeting interleukin-1 in the treatment of rheumatoid arthritis. Arthritis Rheum. 46, 574–578 (2002).
Google Scholar
Eriksson, K. et al. Effects by periodontitis on pristane-induced arthritis in rats. J. Transl. Med. 14, 311 (2016).
Google Scholar
Seeuws, S. et al. A multiparameter approach to monitor disease activity in collagen-induced arthritis. Arthritis Res. Ther. 12, R160 (2010).
Google Scholar
McQuin, C. et al. CellProfiler 3.0: next-generation image processing for biology. PLoS Biol. 16, e2005970 (2018).
Google Scholar
McInnes, L., Healy, J., Saul, N. & Großberger, L. UMAP: uniform manifold approximation and projection. J. Open Source Softw. 3, 861 (2018).
