Table 1.
Randomized control trials of culture-expanded mesenchymal stromal cells
| Author | MSC Tissue Source | Cells/Dose (x106) | Treatment Group Intervention | Control Group Intervention | Sample Size (Treatment/Control) | Male/Female | Baseline Pain Scores (VAS/WOMAC/KOOS) | Follow-up Duration (months) | Follow-up Evaluation |
|---|---|---|---|---|---|---|---|---|---|
| Autologous | |||||||||
| Lee et al. [57] | AT | 100 | sIA injection of MSCs in 3 mL of saline | sIA injection of 3 mL saline |
24 12/12 |
6/18 |
MSC: 60/NA/NA Control: 56.4/NA/NA |
0, 3, 6 |
WOMAC, VAS, KOOS, ROM, MRI (0, 6 months) |
| Freitag et al. [58] | AT | 100 | sIA injection of MSCs or 2 IA injections of MSCs at 0 and 6 months each suspended in 3 mL of saline | Ongoing conventional conservative management only |
30 20/10 |
16/14 |
sIA MSC: NA/59.6/53 dIA MSC: NA/54.4/52.1 Control: NA/58.8/52.8 |
0, 1, 3, 6, 12 |
NPRS, KOOS, WOMAC, MOAKS (0, 12 months) |
| Lamo-Espinosa et al. [59] | M | 100 | sIA injection of MSCs suspended in 3 mL of Ringers Lactate solution followed by weekly injections of PRP (PRGF®), weekly, for 3 weeks (final volume of 8 mL) | sIA injection of PRP (PRGF®), weekly, for 3 weeks (final volume of 8 mL) |
56 28/28 |
33/18 |
MSC: 5.3/33.4/NA Control: 5/31.9/NA |
0, 3, 6, 12 |
VAS, WOMAC, WORMS (0, 12 months) |
| Lamo-Espinosa et al. [56, 60] | M | 10, 100 | sIA injection of low dose or high dose MSCs suspended in 1.5 or 3.0 mL of Ringers Lactate solution, respectively. Both followed by a sIA injection of 4 mL HA (Hyalone®) | sIA injection of 60 mg HA (Hyalone®) in a final volume of 4 mL |
30 20/10 |
17/8 |
10-MSC: 7/37/NA 100-MSC: 6/28/NA Control: 5/29/NA |
0, 3, 6, 12, 48 |
VAS, WOMAC, OARSI, WORMS (0, 6, 12 months) |
| Lu et al. [61] | AT | 50 | 2 IA injections of MSCs at 0 and 3 weeks, SHAM injections at week 1 and 2, suspended in 2.5 mL | 4 IA injections of 2.5 mL HA (week 0, 1, 2, and 3) |
52 26/26 |
6/46 |
MSC: R 5.50, L 5.27/33.77/NA Control: R 4.96, L 4.92/32.15/NA |
0, 6, 12 |
WOMAC, VAS, SF-36, MRI (0, 6, 12 months) |
| Emadedin et al. [63] | M | 40 | sIA injection of MSCs in 5 mL of saline | sIA injection of 5 mL saline |
47 31/39 |
27/16 |
MSC: NA/NA/NA Control: NA/NA/NA |
0, 3, 6 | VAS, WOMAC, MCII, PASS |
| Bastos et al. [62] | M | 40 | sIA injection of MSCs in either 10 mL of PRP or PBS | sIA injection of corticosteroid (4 mg dexamethasone) |
47 30/17 |
24/23 |
MSC: NA/NA/30.3 MSC-PRP: NA/NA/37.3 Control: NA/NA/36.9 |
0, 1, 2, 3, 6, 9, 12 | KOOS, ROM |
| Wong et al. [64] | AT | 14.6 | HTO + Microfracture + sIA injection of MSC suspended in 2 mL of HA | HTO + Microfracture + sIA injection of 2 mL HA |
56 28/28 |
29/27 |
MSC: NA/NA/NA Control: NA/NA/NA |
0, 6, 12, 24 | IKDC, Lysholm, Tegner, MOCART (0, 12 months) |
| Koh et al. [71] | AT | 4.11 | HTO + sIA injection of MSCs suspended in 3 mL of PRP | HTO + sIA injection of 3 mL PRP |
52 26/26 |
11/33 |
Control: 45.4/NA/NA MSC: 44.3/NA/NA |
0, 3, 12, 14–24 |
KOOS, Lysholm, VAS, Radiograph (0, 24 months) |
| Allogeneic | |||||||||
| Gupta et al. [65] | M | 25, 50, 75, 150 | sIA injection of MSCs suspended in 2 mL (25 & 50) or 4 mL (75 and 150) of PLASMA-LYTE A + 20 mg (2 mL) HA | sIA injection of either 2 or 4 mL PLASMA-LYTE A |
60 40/20 |
15/45 |
25-MSC: 60.9/1315.8/NA 50-MSC:73.7/1498.4/NA Control-2: 61.0/1239.6/NA 75-MSC: 57.4/1470.6/NA 150-MSC: 46.6/1388.1/NA Control-4: 65.3/1382.0/NA |
0, 1, 3, 6, 12 |
VAS, ICOAP, WOMAC Index MRI (0, 6, 12 months) |
| Chen & Hu et al. [66] | AT | 16, 32, 64 | sIA injection of MSCs suspended in 8 × 106 cells/mL with cryoprotectant CryoStor® CS10 | sIA injection of Hya Joint Plus 3 mL synovial fluid supplement |
57 49/8 |
11/46 |
MSC: NA/NA/NA Control: NA/NA/NA |
0, 1, 3, 6, 9, 12 | WOMAC, VAS, KSCRS |
| Soltani et al. [67] | Placenta | 50–60 | sIA injection of MSCs suspended in 10 mL of culture media | sIA injection of 10 mL saline |
20 10/10 |
2/18 |
MSC: NA/NA/NA Control: NA/NA/NA |
0, 2, 6 |
VAS, KOOS, ROM, MRA (0, 6 months) |
| Vega et al. [68] | M | 40 | sIA injection of MSCs suspended in 8 mL of Ringer-lactate | sIA injection of 60 mg HA |
30 15/15 |
11/19 |
MSC: 54/41/NA Control: 64/45/NA |
0, 6, 12 |
VAS, WOMAC, Lequesne SF-12, MRI (0, 6, 12 months) |
| Matas et al. [69] | WJ | 20 | 2 IA injection of MSCs at 0 and 6 months or 1 IA injections of MSCs at 0 months and IA injection of saline at 6 months | 2 IA injection of HA at 0 and 6 months |
29 21/8 |
11/18 |
sIA MSC: 44.8/37.4/NA dIA MSC: 39.4/35.6/NA Control: 38.7/28.9/NA |
0, 1, 2, 3, 6, 9, 12 |
WOMAC, VAS, SF-36, WORMS (0, 6, 12 months) |
| Kuah et al. [70] | AT | 3.9, 6.7 | sIA injection of MSCs suspended in 2 mL | sIA injection of cell supernatant |
20 16/4 |
12/8 |
3.9-MSC: 57/6.6/NA 6.7-MSC: 60.8/7.9/NA Control: 43.8/6.3/NA |
0, 1, 3, 6, 9, 12 |
VAS, WOMAC, AQoL-4D, MRI (0, 12 months) |
M bone marrow, AT adipose tissue, WJ Wharton’s jelly, sIA single intra-articular injection, dIA double intra-articular injection, HA hyaluronic acid, PRP platelet-rich plasma, KOOS knee injury and osteoarthritis outcome score, VAS visual analog scale, ROM range of motion, MOAKS MRI osteoarthritis knee score, IKDC International Knee Documentation Committee, MRI magnetic resonance imaging, WOMAC Western Ontario McMaster Universities Arthritis Index, MOCART magnetic resonance observation cartilage repair tissue, MCII minimally clinically important improvement, PASS patient acceptable symptom state, KSCRS new Knee Society Clinical Rating System, WORMS whole-organ magnetic resonance imaging score, HTO high tibial osteotomy, PBS phosphate-buffered saline, MSC mesenchymal stromal cell, ICOAP intermittent and constant pain score, SF-36 36-Item Short Form Survey, SF-12 12-Item Short Form Health Survey, AQoL-4D assessment of quality of life 4D questionnaire, NPRS numeric pain rating scale