Collagen morphology influences macrophage shape and marker expression in vitro

Vasse, Gwenda F.; Kühn, Philipp; Zhou, Qihui; Bhusari, Shardul A.; Reker‐Smit, Catharina; Melgert, Barbro N.; Rijn, Patrick van

doi:10.1016/j.regen.2018.01.002

Cited by 17 publications

(26 citation statements)

References 37 publications

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“…A recent report suggested that MHC-II expression is regulated via exogenous mechanical signals by activation of the p38 MAPK pathway [32] which might explain the differential gene expression of MHC-II in our case. fibrous form at the microscopic level, as reported [36]. This suggests that CD206 expression is sensitive to the biophysical changes of cellular microenvironments.…”

Section: Dense Matrix Enhanced Expression Of Mhc-ii Cd163 and Cd206supporting

confidence: 74%

“…However, we found upregulation of CD206 gene expression in dense collagen matrix in all macrophages. The expression level of CD206 was reported to be correlated to collagen morphology, because collagen can exist in the globular or fibrous form at the microscopic level, as reported [36]. This suggests that CD206 expression is sensitive to the biophysical changes of cellular microenvironments.…”

Section: Dense Matrix Enhanced Expression Of Mhc-ii Cd163 and Cd206mentioning

confidence: 72%

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Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Sapudom¹,

Mohamed

Garcia-Sabaté³

et al. 2020

Bioengineering

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Monocytes circulate in the bloodstream, extravasate into the tissue and differentiate into specific macrophage phenotypes to fulfill the immunological needs of tissues. During the tissue repair process, tissue density transits from loose to dense tissue. However, little is known on how changes in tissue density affects macrophage activation and their cellular functions. In this work, monocytic cell line THP-1 cells were embedded in three-dimensional (3D) collagen matrices with different fibril density and were then differentiated into uncommitted macrophages (MPMA) using phorbol-12-myristate-13-acetate (PMA). MPMA macrophages were subsequently activated into pro-inflammatory macrophages (MLPS/IFNγ) and anti-inflammatory macrophages (MIL-4/IL-13) using lipopolysaccharide and interferon-gamma (IFNγ), and interleukin 4 (IL-4) and IL-13, respectively. Although analysis of cell surface markers, on both gene and protein levels, was inconclusive, cytokine secretion profiles, however, demonstrated differences in macrophage phenotype. In the presence of differentiation activators, MLPS/IFNγ secreted high amounts of IL-1β and tumor necrosis factor alpha (TNFα), while M0PMA secreted similar cytokines to MIL-4/IL-13, but low IL-8. After removing the activators and further culture for 3 days in fresh cell culture media, the secretion of IL-6 was found in high concentrations by MIL-4/IL-13, followed by MLPS/IFNγ and MPMA. Interestingly, the secretion of cytokines is enhanced with an increase of fibril density. Through the investigation of macrophage-associated functions during tissue repair, we demonstrated that M1LPS/IFNγ has the potential to enhance monocyte infiltration into tissue, while MIL-4/IL-13 supported fibroblast differentiation into myofibroblasts via transforming growth factor beta 1 (TGF-β1) in dependence of fibril density, suggesting a M2a-like phenotype. Overall, our results suggest that collagen fibril density can modulate macrophage response to favor tissue functions. Understanding of immune response in such complex 3D microenvironments will contribute to the novel therapeutic strategies for improving tissue repair, as well as guidance of the design of immune-modulated materials.

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Section: Dense Matrix Enhanced Expression Of Mhc-ii Cd163 and Cd206supporting

confidence: 74%

Section: Dense Matrix Enhanced Expression Of Mhc-ii Cd163 and Cd206mentioning

confidence: 72%

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Sapudom¹,

Mohamed

Garcia-Sabaté³

et al. 2020

Bioengineering

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“…Similarly, comparison of hyaluronic acid hydrogels to hyaluronic acid–gelatin hydrogels identified more attachment of peripheral blood‐derived monocytes to the hyaluronic acid–gelatin hydrogels, due to the higher number of cell‐binding motifs in the latter [45]. Moreover, coating surfaces with collagen type I induced polarization of alveolar macrophages towards a more anti‐inflammatory MHCII Lo ‐CD206 Hi phenotype compared with macrophages cultured on uncoated surfaces [46]. Similarly, in an in vitro experiment with mouse bone marrow‐derived macrophages, a collagen type I coating yielded more arginase‐1‐producing macrophages compared with fibronectin‐coated surfaces, suggesting differential effects of distinct ECM proteins probably driven by their distinct cell‐binding domains [26].…”

Section: Biochemical Interactions Between Fibrotic Stroma and Macrophagesmentioning

confidence: 99%

“…However, the number of studies investigating the interactions of these altered structures with macrophages is limited as the post‐translational modifications observed in fibrosis are not well characterized and are difficult to mimic in vitro . From our own studies and studies in the field of biomaterials, we know that the surface or scaffold topography can modulate macrophage behaviour, but translation into a fibrotic context is challenging [46,67].…”

Section: Macrophage Responses To Biophysical Changesmentioning

confidence: 99%

Macrophage–stroma interactions in fibrosis: biochemical, biophysical, and cellular perspectives

Vasse

Nizamoglu

Heijink

et al. 2021

The Journal of Pathology

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Fibrosis results from aberrant wound healing and is characterized by an accumulation of extracellular matrix, impairing the function of an affected organ. Increased deposition of extracellular matrix proteins, disruption of matrix degradation, but also abnormal post‐translational modifications alter the biochemical composition and biophysical properties of the tissue microenvironment – the stroma. Macrophages are known to play an important role in wound healing and tissue repair, but the direct influence of fibrotic stroma on macrophage behaviour is still an under‐investigated element in the pathogenesis of fibrosis. In this review, the current knowledge on interactions between macrophages and (fibrotic) stroma will be discussed from biochemical, biophysical, and cellular perspectives. Furthermore, we provide future perspectives with regard to how macrophage–stroma interactions can be examined further to ultimately facilitate more specific targeting of these interactions in the treatment of fibrosis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

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“…Macrophages expressing Ym1 appear red-fluorescent due to Ym1-antibody labelling upon excitation at 547 nm (Bujisic and Martinon, 2017;Raes et al, 2005;Vasse et al, 2018). For each sample, 5 randomly chosen images were taken.…”

Section: Ym1 Secretion To Distinguish M1-and M2-phenotypesmentioning

confidence: 99%

Phagocytosis and macrophage polarization on bacterially contaminated dental implant materials and effects on tissue integration

Yuan¹,

Ren²,

Dijk³

et al. 2021

eCM

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Bacterial contamination is hard to avoid during dental implant surgery. Macrophages and their polarisation play a decisive role in bacterial colonisation and tissue integration on bacterially contaminated dental implants. The present study investigated the role of macrophages in stimulating tissue coverage overgrowth of contaminating oral bacteria on polished titanium (Ti-P) and acid-etched zirconium dioxide (ZrO2-MA) dental implant materials. Different co-culture models were employed to determine phagocytosis rates of Streptococcus mitis or Staphylococcus aureus contaminating a dental implant surface and the influence of contaminating bacteria and osteoblasts (U2OS) on macrophage polarisation. S. aureus was phagocytized in higher numbers than S. mitis in bi-cultures on smooth Ti-P surfaces. Contaminating S. mitis stimulated near full polarisation of macrophages from a non-Ym1-expressing- to a Ym1-expressing-phenotype on smooth Ti-P, but on ZrO2-MA both phenotypes occurred. In tri-cultures with U2OS-cells on smooth Ti-P, a larger percentage of macrophages remained in their non-Ym1-expressing, “fighting” M1-like phenotype to clear Ti-P surfaces from contaminating bacteria. On ZrO2-MA surfaces, more macrophages tended towards their “fix- and-repair” M2-like phenotype than on Ti-P surfaces. Surface coverage of smooth, bacterially contaminated Ti-P surfaces by U2OS-cells was more effectively stimulated by fighting, M1-like macrophages than on ZrO2-MA surfaces. Comprehensive guidelines are provided for the development of infection-resistant, dental implant materials, including bacteria, tissue and immune cells. These guidelines point to more promising results for clinical application of Ti-P as compared with ZrO2-MA.

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Collagen morphology influences macrophage shape and marker expression in vitro

Cited by 17 publications

References 37 publications

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair

Macrophage–stroma interactions in fibrosis: biochemical, biophysical, and cellular perspectives

Phagocytosis and macrophage polarization on bacterially contaminated dental implant materials and effects on tissue integration

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