Effect of Hyaluronic Acid Compared to Platelet-Rich Plasma as Adjuvants to Bone Marrow Mesenchymal Stem Cell Treatment of Knee Osteoarthritis: Analysis from Two Clinical Trials

Background: Bone marrow mesenchymal stem cell (BM-MSC) therapy has emerged as a safe and feasible treatment option for patients with knee osteoarthritis (OA). However, the role of adjuvants remains unclear. Our aim was to evaluate the clinical and radiological effects of hyaluronic acid (HA) in comparison to platelet-rich plasma (PRP) as adjuvants to 100 x 106 BM-MSCs in the treatment of knee OA. Methods: We used data from two randomized, parallel-group and controlled clinical trials which tested the efficacy of BM-MSC, previously published in 2016 (Clinical Trials.gov identifier NCT02123368, N degrees EudraCT: 2009-017624-72) and 2020 (Clinical Trials.gov identifier NCT02365142. N degrees EudraCT: 2011-006036-23). Results: Of the 34 patients included in the study, 24 had received 100 x 106 BM-MSCs plus PRP and 10 had received 100 x 106 BM-MSCs plus HA. On average, BM-MSC plus HA showed a higher improvement in VAS for pain [beta-coefficient: -1.25; 95% confidence interval (95% CI):-2.20 to -0.30) than BM-MSC plus PRP (p = 0.01). We also observed that BM-MSC plus HA showed a greater improvement in all the WOMAC subscales scores and in the WOMAC overall score, compared to BM-MSC plus PRP, although these differences were not statistically significant. The Whole-Organ Magnetic Resonance Imaging Score (WORMS) at 12 months was more beneficial with 100 x 106 BM-MSCs plus HA (beta-coefficient: -12.61; 95% CI: -19.71, -5.52) than with BM-MSC plus PRP (p = 0.001). Conclusions: The clinical and radiological outcomes after BM-MSC therapy for knee OA could differ according to the adjuvant employed. HA showed greater clinical effectiveness and fewer instances of articular degeneration than PRP as an adjuvant.