{
  "abstract": "Introduction: Mesenchymal stromal cells exhibit potent immunomodulatory properties and are under active investigation for the treatment of immune-mediated disorders. However, their clinical translation is hindered by the lack of standardized potency assays.\n\nMethods: Here, we established a reproducible mixed lymphocyte reaction platform by systematically optimizing peripheral blood mononuclear cell donor composition, culture conditions, and co-culture ratios to define a robust activation window.\n\nUsing this optimized mixed lymphocyte reaction-based potency assay, we compared bone marrow and adipose-derived mesenchymal stromal cells across independent donor batches.\n\nResults: Both sources of mesenchymal stromal cells effectively suppressed T-cell proliferation, with the adipose-derived source demonstrating greater inhibitory activity under the experimental conditions, while a conserved lower threshold of suppression was observed across both sources. Mesenchymal stromal cells reduced early (CD25+) and late (CD25+ HLA-DR+) T-cell activation, with downregulation of CD25 and HLA-DR emerging as sensitive correlates of functional potency. Notably, bone marrow-derived mesenchymal stromal cells exerted stronger suppression of late-stage HLA-DR+ activation and preferentially inhibited CD8+ T-cell expansion, demonstrating source-dependent immunomodulatory functions. Mechanistically, this suppression was associated with modulation of the PD-1 pathway, characterized by decreased soluble PD-1, increased soluble PD-L1, and induction of soluble PD-L2 by mesenchymal stromal cells. PD-L2 levels inversely correlated with T-cell proliferation in the mixed lymphocyte reaction, supporting a PD-1/PD-L2 regulatory axis linked to mesenchymal stromal cell potency.\n\nConclusion: These findings support a standardized and mechanistically informed mixed lymphocyte reaction-based potency assay framework integrating functional suppression, HLA-DR modulation, and PD-1/PD-L2 pathway signaling as complementary indicators of mesenchymal stromal cell activity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Mahin Nikougoftar Zarif"
    },
    {
      "name": "Katia Lefsihane"
    },
    {
      "name": "Neda Khanlarkhani"
    },
    {
      "name": "Lina Sorvik"
    },
    {
      "name": "Jan Fredrik Talts"
    },
    {
      "name": "Katarina Le Blanc"
    },
    {
      "name": "Nadir Kadri",
      "orcid": "0000-0001-5412-5106"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dp0a01fprzg1n.bib",
  "cited_by": 0,
  "doi": "10.1093/stcltm/szag090",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13738804/",
  "id": "dp0a01fprzg1n",
  "issns": [
    "2157-6564",
    "2157-6580"
  ],
  "landing_url": "https://doi.org/10.1093/stcltm/szag090",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/MED00770"
    ],
    [
      "heading",
      "AcademicSubjects/SCI00960"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1307|Mesenchymal stem cell research"
    ]
  ],
  "openalex": "W7160552441",
  "pdf_url": "https://academic.oup.com/stcltm/article-pdf/15/11/szag090/73133381/szag090.pdf",
  "pmcid": "PMC13738804",
  "pmid": "42986840",
  "published": "2026-11-05",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/dp0a01fprzg1n.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:23:44Z",
      "native_id": "PMC13738804",
      "source": "pmc",
      "url": "https://doi.org/10.1093/stcltm/szag090"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Mesenchymal stem cell research",
      "subfield": "cell-biology"
    }
  ],
  "title": "HLA-DR modulation and PD-1/PD-L2 checkpoint signaling identify a mechanistic potency axis for mesenchymal stromal cell immunosuppression",
  "title_text": "HLA-DR modulation and PD-1/PD-L2 checkpoint signaling identify a mechanistic potency axis for mesenchymal stromal cell immunosuppression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:23:44Z",
  "url": "https://research.draconitic.com/paper/dp0a01fprzg1n",
  "venue": "Stem Cells Translational Medicine",
  "versions": []
}