{
  "abstract": "Mesenchymal stromal cell (MSC) interactions with monocytes/macrophages are central to their therapeutic effects in knee osteoarthritis (KOA); however, mechanisms of these interactions are not fully understood. We hypothesize that MSC soluble factors, particularly interleukin-6 (IL-6) and C-C motif chemokine ligand (CCL2) modulate monocytes in KOA environment. Using healthy donor CD14⁺ monocytes exposed to KOA synovial fluid (SF) in the presence or absence of marrow-derived MSC(M) directly or conditioned medium (CM), we evaluated cell surface markers and signaling via signal transducer and activator of transcription (STAT3), nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and c-Jun Terminal Kinase (JNK); functional responses were measured by secretion of tumor necrosis factor (TNF) and IL-1, and by phagocytosis of pHrodo Red E-coli. CD14⁺ monocytes demonstrated a mixed phenotype in KOA SF with increased CD163, CD206, and unchanged HLA-DR, CD86 marker expression. This was accompanied by activated STAT3, JNK, and NF-κB signaling. TNF and IL-1 secreted levels were unchanged, but phagocytosis was impaired, indicative of a net dysfunctional repair phenotype and functionality. CD14⁺ monocytes in KOA SF were hyporesponsive to additional lipopolysaccharide re-challenge, based on TNF and IL-1 secretion. Addition of MSC(M) to KOA SF programmed CD14⁺ monocytes resolved the dysfunctional phenotype and functionality, with significant increases in CD163, CD206; significant reductions in HLA-DR and CD86 expression; this was accompanied by significantly increased activated STAT3 and decreased activated JNK and NF-κB. TNF and IL-1 secretion were also significantly reduced, and phagocytic capacity restored. Blocking IL-6, or to a lesser extent, CCL2, partially abrogated MSC(M) soluble factor effects. MSC(M) experienced apoptosis in KOA SF; however, apoptotic bodies did not fully recapitulate MSC(M) soluble factor effects. IL-6, CCL2, other soluble factors and apoptotic bodies from MSC(M) secretome mitigate the dysfunctional effects of KOA SF on CD14⁺ monocytes resulting in immunosuppressed phenotype and functionality.",
  "abstract_shown": true,
  "affiliations": [
    "Schroeder Arthritis Institute, University Health Network, Toronto, ON, M5T 0S8, Canada.",
    "Krembil Research Institute, University Health Network, Toronto, ON, M5T 0S8, Canada.",
    "Institute of Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada.",
    "Department of Surgery, Division of Orthopedic Surgery, University of Toronto, Toronto, ON, M5T 1P5, Canada.",
    "Schroeder Arthritis Institute, University Health Network, Toronto, ON, M5T 0S8, Canada. sowmya.viswanathan@uhn.ca.",
    "Krembil Research Institute, University Health Network, Toronto, ON, M5T 0S8, Canada. sowmya.viswanathan@uhn.ca.",
    "Institute of Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada. sowmya.viswanathan@uhn.ca.",
    "Department of Medicine, University of Toronto, Toronto, ON, M5S 3H2, Canada. sowmya.viswanathan@uhn.ca."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mozhgan Rasti"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Aida Feiz Barazandeh"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shahrzad Nouri"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kevin P Robb"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rachel Low"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Oreoluwa Kolade"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kevin Fan"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Rajiv Gandhi"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Sowmya Viswanathan",
      "orcid": "0000-0002-4552-0179"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mjzdykz9c717.bib",
  "cited_by": 1,
  "doi": "10.1038/s41419-026-09194-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13669379",
  "id": "4mjzdykz9c717",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://europepmc.org/article/MED/42875435",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2716|Mesenchymal stem cell research"
    ]
  ],
  "openalex": "W7202354835",
  "pdf_url": "https://europepmc.org/articles/PMC13669379?pdf=render",
  "pmcid": "PMC13669379",
  "pmid": "42875435",
  "published": "2026-08-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4mjzdykz9c717.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:18Z",
      "native_id": "MED:42875435",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42875435"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Mesenchymal stem cell research",
      "subfield": "human-genetics"
    }
  ],
  "title": "Mesenchymal stromal cells immunosuppress osteoarthritis synovial fluid modulated monocytes via IL-6 and CCL2.",
  "title_text": "Mesenchymal stromal cells immunosuppress osteoarthritis synovial fluid modulated monocytes via IL-6 and CCL2.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:18Z",
  "url": "https://research.draconitic.com/paper/4mjzdykz9c717",
  "venue": "Cell death & disease",
  "versions": []
}