The role of adipose-derived stem cells in knee osteoarthritis treatment: insights from a triple-blind clinical study

Abstract

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 (ADMSC) are more accessible and cost-effective. This study aims to evaluate the safety and efficacy of allogeneic ADMSC 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 0.5 × 10⁸ allogeneic ADMSC 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 ADMSC 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, and based on KOOS; quality of life, activity of daily living (ADL), recreation and sports activities, symptom and pain. Although there were no significant changes in ADL, recreation, and sports activities between groups, the ADMSC group showed significant improvements between several follow-up periods. Similar improvements were reported in the ADMSC group between several follow-ups' periods on other scales. Radiological outcomes showed a significant increase in cartilage thickness at specific locations (e.g., middle-lateral patella (P = 0.017), Tibial compartment lateral (P < 0.000)) in the ADMSC group after 6 months, demonstrating the regenerative potential of ADMSC in certain MRA sites. Multivariable analysis underlines the complexity of the interactions among treatment, time, and baseline level of variables. Although ADMSC treatment shows potential for some measures, its effects are not consistently significant for all measures.

Conclusion: Allogeneic ADMSC are safe and effective in reducing pain (based on VAS scale) 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.

Keywords: Triple-blind; Adipose-derived stem cells; Clinical trial; Osteoarthritis; Stem cell.

Fig. 1

Consort diagram. Subjects were randomized to a 1:1 ratio. No patients withdrew from the study after randomization till the end of follow up duration. Cr; Creatinine, KL; kellgren-lawrence, BMI; Body Mass Index