Intra-Articular Injection of Human Bone Marrow-Derived Mesenchymal Stem Cells in Knee Osteoarthritis: A Randomized, Double-Blind, Controlled Trial

Abstract

To assess the impact of a single intra-articular (IA) injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with knee osteoarthritis (OA), a randomized, double-blind, placebo-controlled study was conducted. The study included 24 patients with knee OA who were randomly assigned to receive either a single IA injection of BM-MSCs or normal saline. Changes in the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS) after IA injection were assessed at 3, 6, 9, and 12 months. Magnetic resonance imaging (MRI) with T2 mapping sequences was conducted for knee cartilage assessment at baseline and at 3 and 12 months. The MSC group showed between-group improvement in WOMAC (-5.0 ± 3.6 vs. -0.1 ± 5.5, P = 0.02) and KOOS (23.9 ± 18.3 vs. 7.2 ± 15.9, P = 0.028) scores at 9 months compared with the control group. The MSC group exhibited a less sharp increase in the mean T2 value of the medial compartment than the control group at 12 months, with no serious adverse events observed during follow-up. A single IA injection of allogeneic BM-MSCs provided satisfactory pain relief for patients with knee OA compared with the control group at 9 months. Quantitative T2 MRI mapping of the cartilage showed that IA BM-MSCs could have a preventive effect on OA progression for 12 months. Our findings suggest the potential of allogeneic BM-MSCs IA injection as a pain-relieving and disease-modifying treatment for patients with knee OA in the outpatient setting.

Keywords: intra-articular injection; knee osteoarthritis; mesenchymal stem cells; randomized clinical trial.

Graphical Abstract

Figure 1.

Flow chart of patient enrollment and follow-up. MSC: mesenchymal stem cell; MRI: magnetic resonance imaging.

Figure 2.

Comparison of changes in patient-reported outcomes between groups from baseline to follow-up visits. (a-e) Changes in WOMAC scores; (f-j) Changes in KOOS scores. KOOS: Knee Injury and Osteoarthritis Outcome Score; MSC, mesenchymal stem cell; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; VAS: visual analog scale.

Figure 3.

Comparison of the mean differences and standard deviations from baseline for inflammatory (A, ESR; B, CRP) and bone turnover markers (C, Osteocalcin; D, CTX-I) at each time point between the two groups (*P < 0.05). CRP: C-reactive protein; CTX-I: carboxy-terminal telopeptide of type I collagen; ESR: erythrocyte sedimentation rate.

Figure 4.

Longitudinal analysis of T2 values in three compartments (A, medial; B, lateral; C, patellofemoral) of knee cartilage across MSC and control groups. Each line represents the mean T2 value for each group. The shaded areas delineate the 95% confidence intervals. MSC: mesenchymal stem cell.

Figure 5.

Representative images of quantitative T2 mapping of articular cartilage from control and MSC groups over 12-month follow-up. (A-D) Proton density–weighted images (A) and corresponding T2 maps at baseline (B), 3 months (C), and 12 months (D) from a patient in the control group. The articular cartilage of the medial femoral condyle shows an increase in T2 values over time. (E-H) Proton density–weighted images (E) and corresponding T2 maps at baseline (F), 3 months (G), and 12 months (H) from a patient in the MSC group. The articular cartilage of the medial femoral condyle shows only a mild increase in T2 values over time.