Macrophages Modulate the Function of MSC- and iPSC-Derived Fibroblasts in the Presence of Polyethylene Particles

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dc.creatorGao, Qi
dc.creatorLi, Zhong
dc.creatorRhee, Claire
dc.creatorXiang, Shiqi
dc.creatorMaruyama, Masahiro
dc.creatorHuang, Elijah Ejun
dc.creatorYao, Zhenyu
dc.creatorBunnell, Bruce A.
dc.creatorTuan, Rocky S.
dc.creatorLin, Hang
dc.creatorGold, Michael S.
dc.creatorGoodman, Stuart B.
dc.creator.orcid0000-0001-6196-3722 (Bunnell, Bruce A.)
dc.date.accessioned2022-08-25T15:39:46Z
dc.date.available2022-08-25T15:39:46Z
dc.date.issued2021-11-27
dc.description.abstractFibroblasts in the synovial membrane secrete molecules essential to forming the extracellular matrix (ECM) and supporting joint homeostasis. While evidence suggests that fibroblasts contribute to the response to joint injury, the outcomes appear to be patient-specific and dependent on interactions between resident immune cells, particularly macrophages (Mφs). On the other hand, the response of Mφs to injury depends on their functional phenotype. The goal of these studies was to further explore these issues in an in vitro 3D microtissue model that simulates a pathophysiological disease-specific microenvironment. Two sources of fibroblasts were used to assess patient-specific influences: mesenchymal stem cell (MSC)- and induced pluripotent stem cell (iPSC)-derived fibroblasts. These were co-cultured with either M1 or M2 Mφs, and the cultures were challenged with polyethylene particles coated with lipopolysaccharide (cPE) to model wear debris generated from total joint arthroplasties. Our results indicated that the fibroblast response to cPE was dependent on the source of the fibroblasts and the presence of M1 or M2 Mφs: the fibroblast response as measured by gene expression changes was amplified by the presence of M2 Mφs. These results demonstrate that the immune system modulates the function of fibroblasts; furthermore, different sources of differentiated fibroblasts may lead to divergent results. Overall, our research suggests that M2 Mφs may be a critical target for the clinical treatment of cPE induced fibrosis.
dc.description.sponsorshipThis work was supported by NIH grants UG3TR002136, R01 AR063713, R01 AR073145, the Ellenburg Chair in Surgery at Stanford University, and Lee Quo Wei and Lee Yick Hoi Lun Professorship of The Chinese University of Hong Kong.
dc.identifier.citationGao, Q., Li, Z., Rhee, C., Xiang, S., Maruyama, M., Huang, E. E., Yao, Z., Bunnell, B. A., Tuan, R. S., Lin, H., Gold, M. S., & Goodman, S. B. (2021). Macrophages Modulate the Function of MSC- and iPSC-Derived Fibroblasts in the Presence of Polyethylene Particles. International journal of molecular sciences, 22(23), 12837. https://doi.org/10.3390/ijms222312837
dc.identifier.issn1422-0067
dc.identifier.issue23
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31648
dc.identifier.volume22
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/ijms222312837
dc.rights.holder© 2021 by the authors
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceInternational Journal of Molecular Sciences
dc.subjectfibrosis
dc.subjectmicro physiological system (MPS)
dc.subjectsynovial lining
dc.subject.meshArthroplasty / methods
dc.subject.meshCell Differentiation / drug effects
dc.subject.meshCells, Cultured
dc.subject.meshCoculture Techniques
dc.subject.meshExtracellular Matrix
dc.subject.meshFibroblasts / cytology
dc.subject.meshFibroblasts / drug effects
dc.subject.meshFibroblasts / immunology
dc.subject.meshFibroblasts / metabolism
dc.subject.meshFibrosis / drug therapy
dc.subject.meshFibrosis / immunology
dc.subject.meshFibrosis / metabolism
dc.subject.meshHumans
dc.subject.meshInduced Pluripotent Stem Cells / cytology
dc.subject.meshInduced Pluripotent Stem Cells / drug effects
dc.subject.meshInduced Pluripotent Stem Cells / immunology
dc.subject.meshMacrophages / cytology
dc.subject.meshMacrophages / drug effects
dc.subject.meshMacrophages / immunology
dc.subject.meshMacrophages / metabolism
dc.subject.meshMesenchymal Stem Cells / cytology
dc.subject.meshMesenchymal Stem Cells / drug effects
dc.subject.meshMesenchymal Stem Cells / immunology
dc.subject.meshPolyethylene / pharmacology
dc.titleMacrophages Modulate the Function of MSC- and iPSC-Derived Fibroblasts in the Presence of Polyethylene Particles
dc.typeArticle
dc.type.materialtext

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