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NF?B sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles.

ABSTRACT: Total joint replacement is a highly effective treatment for patients with end-stage arthritis. Proinflammatory macrophages (M1) mediate wear particle-associated inflammation and bone loss. Anti-inflammatory macrophages (M2) help resolve tissue damage and favor bone regeneration. Mesenchymal stem cell (MSC)-based therapy mitigates the M1 dominated inflammatory reaction and favorably modulates the bone remodeling process. In the current study, the immunomodulating ability of (1) unmodified MSCs, (2) MSCs preconditioned by NF?B stimulating ligands [lipopolysaccharide (LPS) plus TNF?], and (3) genetically modified MSCs that secrete IL-4 as a response to NF?B activation (NF?B-IL4) was compared in a macrophage/MSC co-culture system. Sterile or LPS-contaminated ultra-high molecular weight polyethylene particles were used to induce the proinflammatory responses in the macrophages. Contaminated particles induced M1 marker expression (TNF?, IL1?, and iNOS), while NF?B-IL4 MSCs modulated the macrophages from an M1 phenotype into a more favorable M2 phenotype (Arginase 1/Arg 1 and CD206 high). The IL4 secretion by NF?B-IL4 MSCs was significantly induced by the contaminated particles. The induction of Arg 1 and CD206 in macrophages via the preconditioned or naïve MSCs was negligible when compared with NF?B-IL4 MSC. Our findings indicated that NF?B-IL4 MSCs have the "on-demand" immunomodulatory ability to mitigate wear particle-associated inflammation with minimal adverse effects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2744-2752, 2018.

SUBMITTER: Lin T

PROVIDER: S-EPMC6207939 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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NFκB sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles.

Lin Tzuhua T Kohno Yusuke Y Huang Jhih-Fong JF Romero-Lopez Monica M Pajarinen Jukka J Maruyama Masahiro M Nathan Karthik K Yao Zhenyu Z Goodman Stuart B SB

Journal of biomedical materials research. Part A 20180807 10

Total joint replacement is a highly effective treatment for patients with end-stage arthritis. Proinflammatory macrophages (M1) mediate wear particle-associated inflammation and bone loss. Anti-inflammatory macrophages (M2) help resolve tissue damage and favor bone regeneration. Mesenchymal stem cell (MSC)-based therapy mitigates the M1 dominated inflammatory reaction and favorably modulates the bone remodeling process. In the current study, the immunomodulating ability of (1) unmodified MSCs, ( ...[more]

PMID: 30084534

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Project description:Calcium sulfate bone void fillers are increasingly being used for dead space management in infected arthroplasty revision surgery. The presence of these materials as loose beads close to the bearing surfaces of joint replacements gives the potential for them to enter the joint becoming trapped between the articulating surfaces; the resulting damage to cobalt chrome counterfaces and the subsequent wear of ultra-high-molecular-weight polyethylene is unknown. In this study, third-body damage to cobalt chrome counterfaces was simulated using particles of the calcium sulfate bone void fillers Stimulan(®) (Biocomposites Ltd., Keele, UK) and Osteoset(®) (Wright Medical Technology, TN, USA) using a bespoke rig. Scratches on the cobalt chrome plates were quantified in terms of their density and mean lip height, and the damage caused by the bone void fillers was compared to that caused by particles of SmartSet GMV PMMA bone cement (DePuy Synthes, IN, USA). The surface damage from Stimulan(®) was below the resolution of the analysis technique used; SmartSet GMV caused 0.19?scratches/mm with a mean lip height of 0.03?µm; Osteoset(®) led to a significantly higher number (1.62?scratches/mm) of scratches with a higher mean lip height (0.04?µm). Wear tests of ultra-high-molecular-weight polyethylene were carried out in a six-station multi-axial pin on plate reciprocating rig against the damaged plates and compared to negative (highly polished) and positive control plates damaged with a diamond stylus (2?µm lip height). The wear of ultra-high-molecular-weight polyethylene was shown to be similar against the negative control plates and those damaged with third-body particles; there was a significantly higher (p?<?0.001) rate of ultra-high-molecular-weight polyethylene wear against the positive control plates. This study showed that bone void fillers of similar composition can cause varying damage to cobalt chrome counterfaces. However, the lip heights of the scratches were not of sufficient magnitude to increase the wear of ultra-high-molecular-weight polyethylene above that of the negative controls.

Dataset Information

NF?B sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles.

Publications

NFκB sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles.

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