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CD31+ Cell Enrichment Partly Enhances the Therapeutic Effects of Stromal Vascular Fraction in Experimental Primary Osteoarthritis

ABSTRACT: Mesenchymal stromal/stem cell therapy has been extensively studied as a therapeutic strategy for osteoarthritis (OA). However, its clinical translation is hindered by multiple factors, including expansion-related senescence and regulatory hurdles. Stromal vascular fraction (SVF), a less processed and clinically accessible therapeutic option, offers logistical advantages but remains regenerative. We hypothesized that, as a more defined cell population, CD31⁺-enriched SVF (CD31⁺ SVF) would exhibit greater therapeutic efficacy than unselected SVF. To test this hypothesis, we conducted a comparative efficacy study using the Dunkin Hartley guinea pig model of spontaneous OA. Spatial analysis revealed that both treatments modulated extracellular matrix composition in cartilage, including reduced fibronectin and type I collagen levels, with CD31⁺ SVF showing more pronounced effects. Both therapies attenuated cartilage fibrosis, preserved cartilage by increasing aggrecan and suppressing catabolic enzymes such as MMP-13, and reduced inflammation, as evidenced by decreased TNF-α and MCP-1 expression. Notably, these protective effects may involve partially distinct molecular mechanisms. Compared to SVF, CD31⁺ SVF showed greater and more consistent improvements in trabecular bone integrity in OA. These effects may contribute to modulation of the osteochondral unit and warrant further mechanistic investigation.

ORGANISM(S): Cavia porcellus

PROVIDER: GSE305613 | GEO | 2025/12/31

REPOSITORIES: GEO

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Project description:Background: Osteoarthritis (OA) is a highly prevalent degenerative joint disease, yet no effective disease-modifying treatments for OA are clinically available. The anti-inflammatory, immunomodulatory, and tissue regenerative properties of placenta-expanded mesenchymal-like adherent stromal cells (PLX-PAD) address several targets of osteoarthritic disease, suggesting a potential therapeutic role of PLX-PAD in primary OA. Objective: To evaluate the safety and therapeutic efficacy of PLX-PAD cell therapy in primary knee OA (KOA) using the Dunkin Hartley (DH) guinea pig model, with a focus on inflammation, cartilage structure, extracellular matrix (ECM) homeostasis, and subchondral bone remodeling. Methods: PLX-PAD cells were characterized for differentiation capacity, secretome, and immunomodulatory properties in vitro, as well as paracrine effects using ex vivo co-culture with human OA cartilage. Two-month-old healthy animals (n = 10) were used to validate the DH model as a primary KOA model. Six-month-old DH guinea pigs (n = 30) received a single intra-articular (IA) injection of PLX-PAD cells at two different doses or Dulbecco's Phosphate Buffered Saline (DPBS). Safety was assessed via MRI at 7 and 12 months. OA progression and treatment efficacy were evaluated through histological and immunostaining analyses, transcriptomic profiling, and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)-based proteomics, and micro-computed tomography (μCT). Results: PLX-PAD cells exhibited negligible differentiation capacity and secreted anti-inflammatory mediators in vitro, and shifted OA cartilage toward a pro-anabolic, anti-catabolic profile ex vivo. Age-related KOA progression in the DH model was confirmed by histological and molecular comparisons of two-month-old healthy and DPBS-treated animals at twelve months. PLX-PAD treatment reduced joint inflammation and preserved cartilage integrity. Transcriptomic analysis revealed that differentially expressed genes were significantly enriched in inflammatory and catabolic pathways, including TNF and Wnt signaling, along with reduced Adamts4 and Mmp13 expression and protein levels in cartilage following PLX-PAD treatment. MALDI-MSI analysis revealed decreased fibronectin fragmentation and restored ECM peptide distribution in PLX-PAD groups. μCT analysis indicated reduced subchondral bone sclerosis and improved trabecular structure in PLX-PAD-treated animals, with greater improvements in bone mineral density at the higher dose, indicating partial dose-dependent effects. No adverse events were registered. Conclusion: PLX-PAD therapy exhibits disease-modifying effects in primary KOA by attenuating inflammation, preserving cartilage, and improving ECM and bone remodeling at both molecular and structural levels. Clinical investigations are currently underway to explore PLX-PAD’s potential translational applications and long-term efficacy.

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CD31+ Cell Enrichment Partly Enhances the Therapeutic Effects of Stromal Vascular Fraction in Experimental Primary Osteoarthritis

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