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Cell quality attributes, clinical features and biomarker levels influence osteoarthritis patient responses to mesenchymal stromal cells

ABSTRACT: Bone marrow-derived mesenchymal stromal cells (MSC(M)) are promising immunomodulatory therapeutics for osteoarthritis (OA); however, mixed clinical efficacy has been reported. We present new 24-month follow-up data from our previous clinical trial investigating single intra-articular injection of autologous MSC(M) in knee OA, with analysis of responders and non-responders to probe differential baseline disease features and MSC(M) basal fitness. Analysis of patient-reported outcome measures (PROMs) showed responders had greater OA severity at baseline. Lower baseline levels of angiogenic/inflammatory synovial fluid biomarkers correlated to improved PROMs. A gene panel of putative immunomodulatory critical quality attributes (CQAs) distinguished MSC(M) donors classified as responders versus non-responders. Furthermore, an algorithm was developed to rank MSC(M) donors based on in vitro monocyte/macrophage polarization readouts and clinical efficacy. Lastly, microRNA-sequencing of MSC(M) revealed 69 microRNAs associated with responder status. Our data provide evidence for specific clinical phenotype features and biomarkers to stratify OA patients, as well as CQAs for quantifying basal immunomodulatory fitness of MSC(M) in knee OA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE249452 | GEO | 2026/08/06

REPOSITORIES: GEO

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Cell quality attributes, clinical features and biomarker levels influence osteoarthritis patient responses to mesenchymal stromal cells

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