Table 2.
Main variables and outcomes of clinical studies with mesenchymal stem cell therapies.
| Cell Type(s) | Treatment Approach | Dose (×106 Cells) | Regimen (Interval) | Phase | Follow-Up (Years) | N | Age (years) | Defect Size (cm2) | OA Grade | Main Outcome Results | Reference | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PROM/Function | MRI/Arthroscopy | |||||||||||
| Autologous BM-MSCs | Intra-articular injection | 40 | One dose | Pilot | 1 | 12 | 44–54 | NA | II–III | WOMAC a,b: 19.4–8.3 | MRI (PCI) a: 19.5–15.4 | [19] |
| Autologous BM-MSCs | Intra-articular injection | 40 | One dose | I/II | 1 | 15 | 33–64 | NA | II–III | WOMAC a,b: 25–10 | MRI T2 scores a: 59.64–51.14 | [20] |
| Autologous BM-MSCs | Intra-articular injection | 13 | One dose | NA | 2 | 56 | 24–54 | 1.5–9.3 | IV | IKDC a: 33.9–85 (HTO + MSCs) with additional improvement of 7.65 compared to HTO | MRI (MOCART) c: 43.21 (HTO) and 62.32 (HTO + MSCs) with p < 0.001 | [21] |
| Autologous BM-MSCs | Intra-articular injection | 30 | Two doses (1 month) | I/II | 1–2 | 13 | 34–63 | NA | II–III | KOOS (symptoms) a: 67.3–88.7 | MRI a: cartilage thickness: from 2.15–2.16 to 2.38–2.5 (mm) | [22] |
| Autologous BM-MSCs | Intra-articular injection | 8–9 | One dose | NA | 5 | 3 | 54–65 | NA | II–III | VAS a: from 80, 85, and 90 to 45, 8, and 45, respectively | NA | [23] |
| Autologous BM-MSCs | Intra-articular injection (+ HA) | 10 or 100 | One dose | I/II | 4 | 27 | 54–69 | NA | II–IV | WOMAC a,b: 27–27 (control), 37–17 (10 × 106), and 29–16.5 (100 × 106) | NA | [24] |
| Autologous BM-MSCs | Intra-articular injection | 1, 10, or 50 | One dose | I/IIa | 1 | 12 | 40–65 | NA | III–IV | NA | MRI: no changes for T2 scores and WORMSs | [25] |
| Autologous BM-MSCs | Intra-articular injection (+ PRP) | 40 | One dose | I | 1 | 47 | 42–71 | NA | I–IV | KOOS a,b: 36.9–54.4 (corticosteroid), 30.3–54.2 (BM-MSCs), and 37.3–59.9 (BM-MSCs + PRP) | NA | [26] |
| Autologous BM-MSCs | Intra-articular injection | 20 | One dose | I/II | 0.5 | 61 | 43–70 | NA | II–III | WOMAC a,b: 62.61–91.73 (BM-MSCs), and 69.93–72.96 (control) | NA | [30] |
| Autologous BMAC | Intra-articular injection | 0.034 | One dose | NA | 0.5 | 25 | 42–68 | NA | II–IV | VAS a: 3.1–1.5 (BMAC) and 2.9–0.8 (saline) with p = 0.44 | NA | [32] |
| Autologous BMAC | Intra-articular injection | 0.034 | One dose | NA | 0.5–1 | 25 | 42–68 | NA | I–III | VAS c: 1.2 (BMAC) and 0.7 (placebo) with p = 0.98 | MRI (T2 scores) c: 2.4 (BMAC) and 2.5 (placebo) with p = 0.27 | [33] |
| Autologous BMAC | Subchondral bone or intra-articular injections | 0.114 | One dose | NA | 2 | 60 | 48–72 | NA | I–IV | VAS a: 4–1 (subchondral) and 3.5–3.5 (intra-articular) | Defect sizes (cm2) a: from 0.4–5.2 to 1.4–2.9 (subchondral) and no regression (intra-articular) | [34] |
| Autologous BMAC | Subchondral bone injections | 0.156 | One dose | NA | 2–10 | 140 | 65–90 | NA | II–IV | VAS a: 3.5–1.5 (BMAC), and 3.4–2.5 (TKA) | Cartilage volume increase of 2.3% at 2-year follow-up | [35] |
| Autologous AD-MSCs | Intra-articular injection | 10, 50, or 100 | One dose | I/II | 0.5 | 18 | 54–72 | 2–6 | III–IV | WOMAC a,b: 54.2–32.8 (100 × 106) and no improvement (10 and 50 × 106) | Decrease of 40–51% (MRI) and 64% (arthroscopy) in hyaline cartilage defect size | [39] |
| Autologous AD-MSCs | Intra-articular injection | 2, 10, or 50 | One dose | I | 0.5 | 18 | 57–74 | NA | III–IV | WOMAC a,b: 60.7–27.6 (2 × 106), 47.2–24.3 (10 × 106), and 38.8–16.2 (50 × 106) | Possible cartilage improvement in three of six patients | [40] |
| Autologous AD-MSCs | Intra-articular injection | 100 | One dose | IIb | 0.5 | 12 | 55–69 | 0.4–7 | II–IV | WOMAC a,b: 60.0–26.7 | Defect sizes(cm2) a: 3.12–3.15 (MSC) and 3.20–3.56 (control) | [41] |
| Autologous AD-MSCs | Intra-articular injection | 100 | One or two doses (6 months) | NA | 1 | 30 | 44–65 | NA | II–III | WOMAC a,b: 59.0–60.0 (control), 59.6–84.0 (one dose), and 54.4–87.3 (two doses) | MRI (MOAKS): progression of cartilage loss in 67% (control), 30% (one dose), and 11% (two doses) of the participants | [42] |
| Autologous AD-MSCs (SVF) | Intra-articular injection | 15 or 30 | One dose | NA | 0.5–1 | 37 | 41–74 | NA | II–III | WOMAC a,b: 47.1–13.2 (30 × 106), 56.2–21.8 (15 × 106), and 49.3–41.9 (placebo) | No significant difference in cartilage thickness between MSC and control groups | [43] |
| Autologous AD-MSCs | Intra-articular injection | 10, 20, or 50 | Two doses (12 months) | I/IIa | 2 | 18 | 40–70 | NA | II–III | WOMAC a,b: 25.8–8.0 (10 × 106), 49.0–12.4 (20 × 106), and 31.2–12.4 (50 × 106) | MRI a: 23–125 mm3 (cartilage volume) | [44] |
| Autologous AD-MSCs (Re-Join®) | Intra-articular injection | 50 | One dose | IIb | 1 | 52 | 45–64 | NA | I–III | WOMAC a,b: 30.83–21.35 (Re-Join®) and 34.17–27.25 (HA) with p < 0.0005 | MRI: apparent overall increase in cartilage thickness | [45] |
| Autologous AD-MSCs (Re-Join®) | Intra-articular injection | 50 | One dose | IIa | 2 | 30 | 52–70 | 1–8 | III | WOMAC a,b: 40.2–37.3 (MF), 40.9–31.0 (MF + HA), and 45.8–29.0 (MF + HA + Re-Join®) | ICRS-II a: 28.1–27.4 (MF), 27.7–43.2 (MF + HA), and 32.0–55.9 (MF + HA + Re-Join®) | [46] |
| Autologous AD-MSCs | AMI | Not applicable | Not applicable | NA | 2 | 80 | 32–46 | 3–7 | III–IV | KOOS (symptoms) c: 32.3 (group 1) and 27.8 (group 2) with p = 0.005 | MRI (MOCART) c: 62.4 (group 1) and 51.8 (group 2) with p = 0.033 | [48] |
| Autologous AD-MSCs | AMI | Not applicable | Not applicable | NA | 1–2 | 70 | 42–68 | 2.1–9.5 | NA | KOOS (symptoms) c: 67.3 (MSC) and 73.6 (MSC-AC) with p < 0.001 | Higher Kanamiya grades in the MSC-AC group | [49] |
| Allogeneic BM-MSCs | Intra-articular injection | 40 | One dose | I/II | 1 | 30 | 36–73 | NA | II–IV | WOMAC a,b: 45–41 | MRI (PCI) a: 14–9.5 (MSCs) and 15.5–12.5 (HA) with p < 0.05 at 1 year | [28] |
| Allogeneic BM-MSCs (Stempeucel®) | Intra-articular injection | 25, 50, 75, or 150 | One dose | II | 1 | 60 | 47–67 | NA | II–III | WOMAC a,b: 1315.8–717.8 (25 × 106), 1498.4–359.9 (50 × 106), and 1239.6–233.8 (control) | MRI (WORMS) a: 67.0–66.1 (25 M), 78.8–78.0 (50 M), and 76.5–74.9 (control) | [29] |
| Allogeneic AD-MSCs (AlloJoin®) | Intra-articular injection | 10, 20, or 50 | Two doses (3 months) | I | 1 | 22 | 49–65 | NA | II–III | WOMAC a,b: 48.00–24.29 (10 × 106), 42.13–25.63 (20 × 106), and 40.14–29.43 (50 × 106) | MRI a: 10.34–54.58 mm3 of total cartilage volume increase (low dose) | [47] |
| Allogeneic AD-MSCs | Intra-articular injection | 10, 20, or 50 | One dose | I/IIa | 1 | 18 | 40–70 | NA | II–III | WOMAC a,b: 38.83–24.33 (50 × 106), 48.83–23.17 (20 × 106), and 46.17–27.50 (10 × 106) | MRI (T1rho) a: 41.55–38.82 (high dose), 39.30–37.48 (mid-dose), and 38.91–37.94 (low dose) | [50] |
| Allogeneic AD-MSCs | Intra-articular injection | 16, 32, or 64 | One dose | I/II | 1 | 57 | 51–79 | NA | II–III | WOMAC a,b: 41.50–25.75 (HA), 42.88–22.53 (16 × 106), 46.41–18.65 (32 × 106), and 35.27–13.40 (64 × 106) | NA | [51] |
| Autologous SD-MSCs | MAMI | Not applicable | Not applicable | NA | 2 | 14 | 18–46 | 2.1–4.3 | NA | KOOS (symptoms) a,c: 66.33–89.80 (MAMI) and 67.46–83.67 (MACI) with p = 0.015 | MRI (graft infill, score 1–4)a: 2.93–3.86 (MAMI) and 2.64–3.29 (MACI) with p = 0.005 from 3 to 6 months | [52] |
| Allogeneic hUCB-MSCs | Intra-articular injection (+ HA) | 12–20 | One dose | I/II | 0.5–7 | 7 | 29–77 | 4.6–8.1 | III–IV | IKDC a: 39.1–63.2 (6 months) | MRI ΔR1 index of 1.44 (3 years) | [54] |
| Allogeneic hUCB-MSCs | Intra-articular injection (+ HA) | 10 | One dose | NA | 1 | 29 | 48–68 | NA | I–IV | WOMAC a: 22.55–13.46 (mild OA) and 27.57–16.42 (severe OA) | MRI (medial T2 map) a: 58.72–62.58 (mild OA) and 201.57–68.97 (severe OA) | [55] |
| Allogeneic PLMSCs | Intra-articular injection | 50–60 | One dose | Pilot | 0.5 | 20 | NA | NA | II–IV | KOOS (symptoms) c: 41.10 (PLMSCs) and 38.80 (control) | MRI a: Increase in chondral thickness: 2.7 to 3.5 mm | [56] |
| Autologous PBMSCs | Intra-articular injection (+ HA) | NA | NA | IIb | 2 | 120 | 23–55 | ≥3 | III–IV | IKDC a: 42.7–48.1 (control) and 43.1–65.6 (intervention) | MRI (MOCART) a: 10.9–15.6 (control) and 13.1–54.0 (intervention) | [53] |
| Allogeneic BM-MSCs | ACI + BM-MSCs | Not applicable | Not applicable | I/II | 1.5 | 35 | 22–38 | 2–5 | NA | KOOS a,b: 57.9–85.4 | MRI (T1rho) c: 43.1 (healthy control) and 47.9 (repaired cartilage) | [37] |
| Allogeneic BM-MSCs | ACI + BM-MSCs | Not applicable | Not applicable | I/II | 5 | 35 | 22–38 | 2–5 | NA | KOOS a,b: 57.9–78.9 | NA | [38] |
NA: not available; a: means from the baseline to the follow-up; b: overall mean of subscales; c: only means of experimental and control groups; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; KOOS: Knee Injury and Osteoarthritis Outcome Score; IKDC: International Knee Documentation Committee Scores; PCI: poor cartilage index; HTO: high tibial osteotomy; VAS: visual analog score; WORMSs: whole-organ MRI scores; HA: hyaluronic acid; BMAC: bone marrow aspirate concentrate; AMI: autologous mesenchymal stem cell implantation; MAMI: matrix-assisted autologous mesenchymal stem cell implantation; SVF: autologous stromal vascular fraction; MOAKS: MRI osteoarthritis knee scores; and PRP: platelet-rich plasma.