The Role of Adipose-Derived Stem Cells in Knee Osteoarthritis Treatment: Insights from a Triple-Blind Clinical Study

Background: Osteoarthritis (OA) is a degenerative joint disease that primarily affects older adults, characterized by cartilage degradation, synovitis, and osteophyte formation. Despite its prevalence, no medical treatment can reverse the joint cartilage degradation, leading many patients to undergo invasive procedures such as arthroplasty. Mesenchymal stem cells (MSCs), particularly those derived from adipose tissue, have emerged as a promising therapeutic approach due to their ability to differentiate into chondrocytes and potentially regenerate cartilage. While MSCs from bone marrow and umbilical cord have shown efficacy in treating OA, adipose-derived MSCs are more accessible and cost-effective. This study aims to evaluate the safety and efficacy of allogeneic adipose-derived MSCs in treating knee OA. Methods: This triple-blind, interventional clinical trial included 20 patients with idiopathic knee OA, meeting the American College of Rheumatology (ACR) criteria. Patients were randomly assigned to receive an intra-articular injection of either 8.5×10^6 allogeneic adipose-derived MSCs or saline (control group). Participants were evaluated for clinical signs of inflammation at baseline, and then at 2 weeks, 2 months, and 6 months post-injection using clinical assessments, the Visual Analogue Scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), range of motion (ROM), and Magnetic Resonance Arthrography (MRA). Results: The MSC group exhibited significant improvement in pain reduction as measured by VAS scores compared to the control group (P < 0.05). However, no significant differences were observed between the groups in ROM, quality of life, or daily activities as assessed by KOOS. Radiological outcomes showed a significant increase in cartilage thickness at specific locations (e.g., MLP, TCL) in the MSC group after 6 months, demonstrating the regenerative potential of MSCs in certain MRA sites. Conclusion: Allogeneic adipose-derived MSCs are safe and effective in reducing pain and increasing cartilage thickness in knee OA patients. However, they do not significantly enhance quality of life or daily activity compared to placebo. Further research with larger sample sizes and longer follow-up periods is needed to confirm these findings and determine optimal dosing strategies. Trial registration: Trial Registry Code: IRCT2016021123298N3, 20 February 2016. https://irct.behdasht.gov.ir/trial/19909