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Polypropylene mesh implantation for hernia repair causes myeloid cell–driven persistent inflammation
Felix Heymann, … , Ulf P. Neumann, Frank Tacke
Felix Heymann, … , Ulf P. Neumann, Frank Tacke
Published January 24, 2019
Citation Information: JCI Insight. 2019;4(2):e123862. https://doi.org/10.1172/jci.insight.123862.
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Research Article Gastroenterology Inflammation

Polypropylene mesh implantation for hernia repair causes myeloid cell–driven persistent inflammation

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Abstract

Polypropylene meshes that are commonly used for inguinal hernia repair may trigger granulomatous foreign body reactions. Here, we show that asymptomatic patients display mesh-associated inflammatory granulomas long after surgery, which are dominated by monocyte-derived macrophages expressing high levels of inflammatory activation markers. In mice, mesh implantation by the onlay technique induced rapid and strong myeloid cell accumulation, without substantial attenuation for up to 90 days. Myeloid cells segregated into distinct macrophage subsets with separate spatial distribution, activation profiles, and functional properties, showing a stable inflammatory phenotype in the tissue surrounding the biomaterial and a mixed, wound-healing phenotype in the surrounding stromal tissue. Protein mass spectrometry confirmed the inflammatory nature of the foreign body reaction, as characterized by cytokines, complement activation, and matrix-modulating factors. Moreover, immunoglobulin deposition increased over time around the implant, arguing for humoral immune responses in association with the cell-driven inflammation. Intravital multiphoton microscopy revealed a high motility and continuous recruitment of myeloid cells, which is partly dependent on the chemokine receptor CCR2. CCR2-dependent macrophages are particular drivers of fibroblast proliferation. Thus, our work functionally characterizes myeloid cell–dependent inflammation following mesh implantation, thereby providing insights into the dynamics and mechanisms of foreign body reactions to implanted biomaterials.

Authors

Felix Heymann, Klaus-Thilo von Trotha, Christian Preisinger, Petra Lynen-Jansen, Anjali A. Roeth, Melanie Geiger, Lukas Jonathan Geisler, Anna Katharina Frank, Joachim Conze, Tom Luedde, Christian Trautwein, Marcel Binnebösel, Ulf P. Neumann, Frank Tacke

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Figure 3

Flow cytometry profiling of myeloid cells at day 7 and day 21 after mesh implantation in mice.

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Flow cytometry profiling of myeloid cells at day 7 and day 21 after mesh...
Flow cytometric characterization of mesh explants: t-SNE flow cytometry analysis of murine mesh explants at day 7 (A) and day 21 (B) after implantation. Cells were pregated on CD45+Ly6G– cells and subjected to unbiased t-SNE analysis. Overlays were generated from mesh- and sham-operated animals, and the clusters were then analyzed in detail for their marker expression profiles, as shown in the subsequent histogram overlays. MAM, mesh-associated macrophage; SIM, stroma-infiltrating macrophage. (C) Cytokine production from myeloid cells isolated from mesh-associated tissue. Cells were pregated on CD45+Ly6G–F480+CD11b+. (D) Phenotyping of TNF+ cells pregated on CD45+Ly6G–. Exemplary results are shown in the dot plots; statistical analysis was performed from ≥5 animals per group. Student’s t test: *P < 0.05; ***P < 0.001. Error bars represent mean ± SD.

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