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

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

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