ArticleFrontiers in bioengineering and biotechnology2025
Innate immune pathway activation to modulate mesenchymal stromal cell (MSC) interactions with synovium and cartilage.
Article in Frontiers in bioengineering and biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Cord blood mesenchymal stromal cells combined with hyaluronic acid show symptom-modifying and potential disease-modifying effects in an equine osteoarthritis fetlock chip model.Frontiers in veterinary science · 2026Article
- C-1101 multi-protein platelet and plasma-derived therapeutic to treat chronic lumbosacral radiculopathy.Frontiers in bioengineering and biotechnology · 2026Article
- Multiple strategies, one mission: mesenchymal stromal cell-based mechanisms of action in osteoarthritis.Frontiers in cell and developmental biology · 2026Review
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7 authors.
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Abstract
Introduction: Mesenchymal stromal cells (MSCs) have been evaluated as a local therapeutic option to treat osteoarthritis (OA) with conflicting clinical results. Our previous studies have evaluated immune licensing of MSC through activation of Toll-like receptor and cytosolic cGAS-STING pathways, with demonstrated improvement in functional and structural outcomes in a rodent model of OA. The objective of this study was to investigate impact of MSC activation on their interaction with relevant joint target cells to better understand the mechanisms by which pre-activation improves MSC activity for treatment of osteoarthritis. Methods: Equine bone-marrow-derived MSCs (passage 2-3) from 3 healthy donors were stimulated with a TLR3-pathway agonist (polyinosinic:polycytidylic acid) or STING pathway agonist (2'3'-cGAMP) (10 μg/mL, 2 h, 2 × 10 Results: TLR-MSC-CM decreased IL-1β (p = 0.02), IL-6 (p = 0.02) secretion by synoviocytes and IL-18 secretion by activated chondrocytes (p = 0.002). STING-MSC-CM decreased IL-6, IL-8 secretion (p = 0.08) by synoviocytes, decreased IL-8 (p = 0.05) by activated chondrocytes, increased G-CSF (p = 0.01), IL-4 (p = 0.01) and decreased IL-5 (p = 0.01) by activated macrophages. Transcriptomic analyses indicated differential gene expression in each cell line following CM treatment varied by cell line. STING-MSC-CM vs TLR-MSC-CM induced 38 significantly altered DEGs in synoviocytes, 20 in chondrocytes, and 47 in macrophages. Discussion: These findings indicate that joint cells respond differently to factors secreted by TLR or STING pathway activated MSC. The pathways altered were different for each target cell type and no clear pattern of responses was apparent. These results indicate that
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