CD31 ⁺ Cell Enrichment Enhances Therapeutic Effects of Stromal Vascular Fraction in Experimental Primary Osteoarthritis: A Preclinical Study in the Dunkin Hartley Guinea Pig Model

ABSTRACT Despite the growing burden of osteoarthritis (OA), effective disease‐modifying treatments remain limited. Hyaluronic acid, platelet‐rich plasma, and hydrogels are in clinical use, but their efficacy beyond placebo is debated. Cell‐based therapies are continuously investigated for their disease‐modifying potential. Stromal vascular fraction (SVF), a minimally processed and clinically accessible cell product, has shown therapeutic potential, but remains poorly characterized in respect to its pro‐regenerative cell types and molecular signaling. To determine whether CD31 ⁺ cell enrichment enhances the regenerative efficacy of SVF, a comparative efficacy study was conducted using the Dunkin Hartley guinea pig model of spontaneous OA. Spatial proteomics reveals that both treatments modulate cartilage extracellular matrix (ECM) composition, reducing fibronectin and COL1A1 levels, with CD31 ⁺ SVF showing more pronounced effects. Both therapies attenuate cartilage fibrosis, increase aggrecan, suppress MMP‐13, and reduce TNF‐α and MCP‐1 expression. Compared to SVF, CD31 ⁺ SVF shows greater and more consistent improvements in subchondral and trabecular bone integrity. These findings demonstrate that CD31 ⁺ enrichment enhances the therapeutic potential of SVF, likely through more consistent modulation of ECM remodeling and osteochondral integrity. Our results provide a preclinical rationale for the testing of CD31 ⁺ ‐enriched SVF as a biologically refined cell therapy approach for OA, with potential disease modifying properties.