Table 2.
Clinical effects of culture-expanded mesenchymal stromal cell injections on knee OA cartilage
| Author | MSC tissue source | Cell dose (x106 cells) | Treatment group intervention | Comparison (baseline or control) | Number treated | Cartilage outcome measures | Time points | Cartilage outcomes |
|---|---|---|---|---|---|---|---|---|
| Autologous | ||||||||
| Jo et al. [45] | AT | 10, 50, 100 | sIA injection of MSC | Baseline |
12 (100 × 106 dose); 3 (50 × 106 dose); 3 (10 × 106 dose) |
MRI (volume, defect size), Arthroscopy, Histology (Col I, Col II, SafO), X-ray (KL, JSW) |
0, 3, 6 months (MRI, X-ray); 0, 6 months (arthroscopy, histology) |
Regeneration favouring high-dose group by MRI, arthroscopy, histology |
| Lamo-Espinosa et al. [60] | M | 10, 100 | sIA injection of MSC + 60 mg HA | Baseline, 60 mg HA control |
10 (100 × 106 dose); 10 (10 × 106 dose); 10 (control) |
MRI (WORMS), X-ray (JSW) | 0, 6, 12 months | Possible regeneration favouring high-dose group by X-ray and MRI |
| Freitag et al. [58] | AT | 100 | sIA injection of MSC ± second injection at 6 months | Baseline, conservative management control, and dose groups |
10 (single dose); 10 (two doses); 10 (control) |
MRI (MOAKS) | 0, 12 months | Chondroprotection favouring two-dose group |
| Lamo-Espinosa et al. [59] | M | 100 | IA injections of MSC at 0, 1, and 2 weeks + 8 mL PRP | Baseline, PRP only control |
30 (MSC+PRP); 30 (control) |
MRI (WORMS), X-ray (JSW) | 0, 12 months | No significant effects |
| Lee et al. [57] | AT | 100 | sIA injection of MSC | Baseline, 3 mL saline (vehicle) control |
12 (MSC group); 12 (control) |
MRI (volume, defect size), X-ray (KL, JSW, HKA) | 0, 6 months | Chondroprotection; significant increase in defect size observed in saline- but not MSC-treated group by MRI |
| Song et al. [126] | AT | 10, 20, 50 | Bilateral IA injections of MSC at 0, 3 weeks ± third injection at 48 weeks | Baseline | 6/dose group | MRI (volume) | 0, 12, 24, 48, 72, 96 weeks | Regeneration favouring high-dose group with subsequent reduction in cartilage volume at 96 weeks |
| Chahal et al. [119] | M | 1, 10, 50 | sIA injection of MSC | Baseline |
4 (50 × 106 dose); 4 (10 × 106 dose); 4 (1 × 106 dose) |
MRI (T2, WORMS), ELISA (HA, COMP, C1–2C, C2C, CTXII) |
0, 6, 12 months (MRI); 2, 6, 12, 24, and 48 week (ELISA) |
Possible chondroprotection; no changes by MRI but catabolic biomarkers were significantly reduced and favoured high-dose group |
| Chen et al. [127] | AT | 50 | sIA injection of MSC | Baseline | 12 | MRI (MOAKS), X-ray (KL, JSW) | 0, 48 weeks | Regeneration indicated by reduced MOAKs articular cartilage pathology scores |
| Lu et al. [61] | AT | 50 | Bilateral IA injections at 0 and 3 weeks | Baseline, 25 mg HA control | 26/group | MRI (volume) | 0, 24, 48 weeks | Regeneration in MSC group with degeneration in HA group |
| Orozco et al. [128] | M | 40 | sIA injection of MSC | Baseline | 12 | MRI (T2, PCI) | 0, 6, 12 months | Regeneration indicated by significant reduction in PCI scores at 6 and 12 months |
| Rich et al. [129] | M | 40 | sIA injection of MSC | Baseline | 50 | MRI (T2, PCI) | 0, 12 months | Regeneration indicated by significant reduction in T2 values |
| Soler et al. [130] | M | 40 | sIA injection of MSC | Baseline | 15 | MRI (T2, PCI) | 0, 6, 12 months | Regeneration indicated by significant reduction in T2 values at 6 and 12 months |
| Al-Najar et al. [131] | M | 30.5 | IA injection of MSC at 0 and 1 month | Baseline | 13 | MRI (thickness) | 0, 6, 12 months | Regeneration indicated by increased cartilage thickness at 12 months |
| Allogeneic | ||||||||
| Gupta et al. [65] | M | 25, 50, 75, 150 | sIA injection of MSC + 20 mg HA | Baseline, vehicle + HA control |
10 (for each MSC dose); 20 (control) |
MRI (WORMS), X-ray (unspecified parameters) |
0, 6, 12 months (MRI); 0, 3, 6 months (X-ray) |
No significant effects |
| Sadri et al. [121] | AT | 100 | sIA injection of MSC | Baseline | 3 | MRI (thickness, volume), ELISA (COMP, HA, CTX-II, MMP-3) |
0, 6 months (MRI); 0, 1 week, 1, 3, 6 months |
Possible chondroprotection and regeneration by MRI and ELISA but small sample size |
| Soltani et al. [67] | Placenta | 50–60 | sIA injection of MSC | Baseline, saline control |
10 (MSC); 10 (control) |
MRA (thickness) | 0, 24 weeks | Regeneration indicated by increased cartilage thickness relative to baseline in MSC but not control group |
| Zhao et al. [132] and Lu et al. [133] | AT | 10, 20, 50 | Bilateral IA injections at 0 and 3 weeks | Baseline |
7 (10 × 106 group); 8 (20 × 106 group); 7 (50 × 106 group) |
MRI (volume, WORMS, T1rho, T2, T2star, R2 star, ADC, FA) | 0, 48 weeks | Regeneration favouring high-dose group |
| Vega et al. [68] | M | 40 | sIA injection of MSC | Baseline, 60 mg HA control |
15 (MSC group); 15 (control) |
MRI (T2, PCI) | 0, 6, 12 months | Regeneration indicated by improved PCI in MSC(M)-treated patients relative to HA at 12 months |
| Matas et al. [69] | WJ | 20 | sIA injection of MSC ± second injection at 6 months | Baseline, 60 mg HA control |
10 (single dose); 10 (two doses); 8 (control) |
MRI (WORMS) | 0, 6, 12 months | No significant effects |
| Park et al. [134] | CB | 11.5–20 | Implantation of HA hydrogel containing MSC(WJ) | Baseline | 6 | MRI (dGEMRIC ΔR1), Arthroscopy, Histology (Col II, SafO) |
0, 3 years (MRI); 0, 12 weeks, 12 months (arthroscopy, histology) |
Possible regeneration but small sample sizes |
| Kuah et al. [70] | AT | 3.9, 6.7 | sIA injection of MSC + cell supernatant | Baseline, control group treated with cell supernatant and vehicle only |
8 (3.9 × 106 dose); 8 (6.7 × 106 dose); 4 (control) |
MRI (volume, MOAKS), ELISA (C2C, CTXII, HA, CTX-I) | 0, 12 months | Chondroprotection within the low-dose group relative to high-dose and control group by MRI but not biomarkers |
M bone marrow, AT adipose tissue, WJ Wharton’s jelly, CB cord blood, sIA single intra-articular injection, HA hyaluronic acid, PRP platelet-rich plasma, MRI magnetic resonance imaging, MOAKS MRI Osteoarthritis Knee Score, MOCART magnetic resonance observation cartilage repair tissue, WORMS whole-organ magnetic resonance imaging score, ADC apparent diffusion coefficient, FA fractional anisotropy, KL Kellgren-Lawrence classification of osteoarthritis, JSW joint space width, HKA hip-knee angle, SafO safranin O, MSC mesenchymal stromal cell, MRA Magnetic resonance arthrogram, dGEMRIC delayed gadolinium-enhanced MRI of cartilage, COL1 collagen type I, COL2 collagen type II, COMP cartilage oligomeric matrix protein, C1-2C C1-2C collagen type I and II cleavage, C2C collagen type II cleavage, CTX-I C‐telopeptide of type II collagen, CTX-II C‐telopeptide of type II collagen, MMP-3 matrix metalloproteinase 3