Clinical Efficacy Of Intra-articular Mesenchymal Stem Cells For The Treatment Of Knee Osteoarthritis: A Double Blinded, Prospective, Randomized, Controlled Clinical Trial

Abstract

Objectives:Currently, there are limited non-operative treatment options available for knee osteoarthritis (OA). Stem cell based therapies have emerged as promising non-operative treatments for knee OA. Various stem cell mediums have been investigated, but there are limited prospective, randomized controlled trials for any of these therapies. This study aimed to investigate the 6 month and 1 year efficacy of intra-articular injections of autologous stromal vascular fraction stem cell therapy (SVF) in a double blinded, prospective, randomized, placebo controlled trial.Methods:This was a multi-site prospective, randomized, double-blinded clinical trial. Adult patients with symptomatic knee OA were eligible for enrollment. Patients were randomized to high dose SVF injection (3.0×107 SVF cells), low dose SVF injection (1.5×107 SVF cells), or placebo injection (zero SVF cells) in a 1:1:1 fashion. SVF was obtained via liposuction, which was then processed and injected during the same clinic visit. Knee function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. MRIs were reviewed for changes in the cartilage thickness of chondral lesions. WOMAC scores and MRIs were obtained before injection, and at 6 and 12 months post-injection. The Wilcoxon Rank Sum non-parametric test was utilized to assess statistical significance and the Hodges-Lehmann Location Shift (HLLS) with confidence intervals was used to assess superiority.Results:A total of 39 participants were enrolled (high dose: 13, low dose: 13, placebo: 13). The median percent change in WOMAC scores from pre-injection to 6 months post-injection for the high dose group, low dose group, and placebo group were 83.9%, 51.5% and 25.0%, respectively. The high dose and low dose groups displayed a significantly greater percent change in WOMAC scores compared to the placebo group (high dose: p=0.04; low dose: p=0.02).The median percent change in WOMAC scores from baseline to 1 year post-injection for the high dose group, low dose group, and placebo group were 89.5%, 68.2%, and 0%, respectively. Similar to the 6 month evaluation, the high dose and low dose groups displayed a greater percent change in 1 year WOMAC scores compared to the placebo group (high dose: p = 0.006, low dose: p = 0.009). The 6-month follow-up MRIs demonstrated no change in cartilage thickness for all subjects. The mean change in cartilage thickness for the treatment group (high dose and low dose) and the placebo group was -0.2mm and 0.5 mm, respectively, with no statistical difference between groups (p= 0·89). During the 12 months post-injection there were no serious adverse events, or evidence of neoplastic growths.Conclusion:Intra-articular injection of both high dose and low dose SVF cells provides significant improvement in knee OA symptoms for at least 1 year post-injection. Knee function in all patients improved during the first 6 months post-injection; however, both high and low dose treatment groups experienced significantly greater improvement than the placebo group. The symptomatic treatment effect was found to be dose dependent. Furthermore, while WOMAC scores continued to improve for both treatment groups during the 6 months to 1 year period, the placebo group returned to baseline during the same time interval. The efficacy of SVF injections, in combination with its safety and ease of use, support its’ use as a treatment option for symptomatic knee osteoarthritis.