Autologous adipose-derived mesenchymal stromal cell injection for knee osteoarthritis improves pain and function without a clear increase in adverse events: A systematic review and meta-analysis of randomized controlled trials

To systematically review randomized controlled trials and quantitatively evaluate the efficacy and safety of injections of autologous adipose-derived mesenchymal stromal cells (AD-MSCs) in patients with knee osteoarthritis (OA). Multiple electronic databases were searched with no date restrictions for randomized controlled trials evaluating intra-articular autologous adipose-derived cell products for knee OA. The stromal vascular fraction was considered biologically distinct and was not pooled for the same intervention. The primary efficacy outcomes were the pain visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores. Safety outcomes were defined by the occurrence of any adverse events (AEs) and serious AEs (SAEs). A random-effects meta-analysis was performed. Of the 1178 identified records, six randomized controlled trials, including 551 patients, were included. Compared with control, AD-MSC treatment was associated with lower WOMAC total scores at 3 months (mean difference [MD], -8.14; 95% confidence interval [CI], -13.33 to -2.95) and 6 months (MD, -8.07; 95% CI, -13.60 to -2.54), and lower pain VAS scores at 3 months (MD, -1.49; 95% CI, -2.45 to -0.54), 6 months (MD, -1.40; 95% CI, -2.08 to -0.73) and 12 months (MD, -1.80; 95% CI, -3.20 to -0.41). The pooled risk of any AEs was not significantly increased (risk ratio [RR], 1.12; 95% CI, 0.99-1.27), and SAEs were rare (RR, 0.48; 95% CI, 0.10-2.18). Intra-articular autologous AD-MSC injections for knee OA were associated with improvements in pain and WOMAC outcomes without a significant increase in AEs. However, given the heterogeneity in comparator type, blinding and cell-product characteristics and the limited long-term and structural evidence, these findings suggest symptomatic benefit across heterogeneous AD-MSC products but do not establish the efficacy of a specific standardized product or structural disease modification. Level I, systematic review and meta-analysis of randomized controlled trials.