Background <p>Osteoarthritis is a common degenerative joint disease marked by cartilage degeneration and inflammation. This study investigates the therapeutic potential of adipose-derived stromal cells (ASCs) and their secretome in a rat model of osteoarthritis.</p> Methods <p>ASCs were extracted from human adipose tissue, cultured, and primed with human platelet lysate. The secretome was collected after 48&#xa0;h of serum-free culture. Osteoarthritis was induced in rats using monosodium iodoacetate, and after 14 days, they were treated with saline solution, ASCs, or secretome. Over five weeks, body weight and histopathological changes were monitored.</p> Results <p>No clinical complications arose post-treatment, and all rats gained weight similarly. ASC treatment increased histopathological changes associated with osteoarthritis, including severe cartilage necrosis and bone remodeling. Conversely, the secretome treatment resulted in mild to moderate cartilage degeneration, similar to that observed in the control group. These findings suggest that ASCs may contribute to disease progression in this model, while the secretome did not show significant effects on cartilage histology compared to the control group. Further studies are needed to determine whether optimizing the secretome composition or dosing could enhance its therapeutic potential.</p> Conclusions <p>This study highlights the complexity of ASC interactions with the immune system, while secretome may be a well-tolerated treatment, further studies are needed to determine its potential therapeutic benefits.</p>