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

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-a 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. Overall design: RNA-seq profiling of knee cartilage and infrapaterllar fat pad from Dunkin Hartley guinea pigs 6 months after receiving intra-articular injections of DPBS or SVF or CD31? SVF.