Table 2.
Stem cell-based therapy for cartilage/osteochondral defect and OA.
| Disease condition | Cell sources | Sample size and group | Placebo/Control | Follow-up | Route of administration | Main results | Study group |
|---|---|---|---|---|---|---|---|
| Cartilage defect | Autologous Chondrocytes | 23 patients (13 femoral condyle defect due to trauma; 3 osteochondritis dissecans; 6 chondromalacia patellae; 1 traumatic origin) | N/A | 39 months (16–66 months) | Autologous chondrocyte implantation | Transplants eliminated knee locking and reduced pain and swelling after surgery. Two-year follow-up showed that 14 (14/16) patients with femoral condylar transplants had good-to-excellent results. Three-year follow-up showed that 2 (2/7) patients with patellar transplants had excellent or good results. |
Brittberg et al., 1994 |
| 224 patients | N/A | 12.8 years (10–20 year) | 92% of the patients were satisfied with the treatment effect, and 74% of the patients reported same or better status as previous years. Improved clinical outcome, better life quality, and high activity level were reported. | Peterson et al., 2010 | |||
| CDPCs | 15 patients | N/A | 12 months | MACI, mini-arthrotomy | The cartilage defects (6–13 cm2) were completely repaired. Knee function (IKDC scores and Lysholm scores) was significantly improved. | Jiang et al., 2016 | |
| BMSCs | 24 patients; BMSCs (n = 12), Placebo (n = 12) | Cell-free collagen gel sheet | 10.5 months (28–95 weeks) | Implantation at the time of HTO | Arthroscopic and histological grading scores were significantly improved, but no significant clinical improvement. | Wakitani et al., 2002 | |
| 3 patients | N/A | 27 months | Transplantation surgery | The cartilage defects were repaired, and clinical symptoms were improved. | Wakitani et al., 2007 | ||
| 1 patient | N/A | 12 months | Arthroscopic surgery | The defect was recovered with hyaline-like cartilage tissue, and clinical symptoms were improved. | Kuroda et al., 2007 | ||
| SMSCs | 10 patients (Symptomatic single cartilage lesion in femoral condyle) | N/A | 52 months (37–80 months) | Arthroscopic surgery | The MRI score and Lysholm score were significantly improved compared to pre-surgery. | Sekiya et al., 2015 | |
| 5 patients (Symptomatic knee chondral lesions; 1.5-3.0 cm2) | N/A | 24 months | Mini-arthrotomy | The defects were successfully repaired. And the VAS, Lysholm, and KOOS scores were significantly improved compared to pre-surgery. | Shimomura et al., 2018 | ||
| Osteoarthritis | Bone marrow aspirate concentrate (BMAC) | 25 patients (bilateral knee OA); BMACs into one knee joint and placebo into the contralateral knee | Sterile saline | 6 months | Intra-articular injection | The pain relief (VAS scores and ICOAP scores) was significant compared to the baseline, but was non-significant compared to the saline treated contralateral knee. | Shapiro et al., 2017; Phase I |
| BMSCs | 60 patients; Cohort1: BMSCs dose1(2.5 × 107 cells; n = 10), Placebo (n = 5); Cohort2: BMSCs dose2 (5 × 107 cells; n = 10), Placebo (n = 5); Cohort3: BMSCs dose3 (7.5 × 107 cells; n = 10), Placebo (n = 5); Cohort4: BMSCs dose4 (1.5 × 108 cells; n = 10), Placebo (n = 5) | PLASMA-LYTE A (a multiple electrolytes injection) | 12 months | Intra-articular injection | The lowest dose cohort (Cohort1; 2.5 × 107 cells) showed a trend toward improvement in all parameters including VAS, WOMAC and ICOAP cores (though non-significant compared to the placebo group), while other higher doses cohorts neither showed significant symptomatic relief, nor showed acceptable safety. | Gupta et al., 2016; Phase II | |
| ADSCs | 52 patients; ADSCs group (n = 26); Placebo (n = 26) | 1% sodium Hyaluronic acid | 12 months | Intra-articular injection | ADSCs group showed significant improvement in joint (WOMAC scores) and cartilage volume (MRI quantification) in comparison with both baseline and placebo group. | Lu et al., 2019; Phase IIb | |
| 18 patients; ADSCs low-dose: (1 × 107 cells; n = 6); ADSCs mid-dose: (2 × 107 cells; n = 6); ADSCs high-dose: (5 × 107 cells; n = 6) | N/A | 24 months | Intra-articular injection | ADSCs group with different dosage all showed significant improvement in joint function (WOMAC scores), life quality (SF-36 scores) and cartilage volume (MRI quantification). The high dose group (5 × 107 cells) exhibited the highest improvement. |
Song et al., 2018; Phase I/II | ||
| 24 patients; ADSCs group (1 × 108 cells; n = 12); Placebo (n = 12) | Sterile saline | 6 months | Intra-articular injection | ADSCs group showed a significant functional improvement and pain relief in comparison with baseline, without cartilage volume changes at 6 months' follow-up. | Lee et al., 2019; Phase IIb | ||
| 30 patients; ADSCs single-injection group: (1 × 108 cells; n = 10); ADSCs twice-injection group: (1 × 108 cells, injection at baseline and 6 months; n = 10); Control group: (n = 10) | Conservative management | 12 months | Intra-articular injection | The pain, function, and life quality of both treatment groups were significantly improved compared to the control group. | Freitag et al., 2019; Phase II | ||
| UC-MSCs | 26 patients; Single-dose UC-MSCs (20 × 106 cells, n = 9); Repeated-dose UC-MSCs (20 × 106 cells, twice a year, n = 9); Placebo (n = 8) | Hyaluronic acid | 12 months | Intra-articular injection | Pain (WOMAC-A, pain scores) and function (WOMAC-C, function scores) were significantly improved in comparison with placebo group. Repeated-dose UC-MSCs (20 × 106cells, twice a year) exhibited a superior effect to placebo group and single-dose group. | Matas et al., 2019; Phase I/II | |
| 6 patients (KL grade 3 and ICRS cartilage defect grade 4); Low-dose group (1.15–1.25 × 107cells; n = 3) High-dose group (1.65–2.0 × 107cells; n = 3) | N/A | 7 years | Intra-articular injection |
The improved clinical outcomes were stable over 7 years of follow-up. The histological findings at 1 year showed hyaline-like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. No cases of osteogenesis or tumorigenesis was observed over 7 years. |
Park et al., 2017; Phase I/II |
ADSCs, adipose-derived mesenchymal stromal cells; BMSCs, Bone marrow-derived mesenchymal stromal cells; CDPCs, Cartilage derived progenitor cells; HTO, High tibial osteotomy; ICOAP, intermittent and constant osteoarthritis pain; ICRS, International Cartilage Repair Society; IKDC, International Knee Documentation Committee; KL, Kellgren-Lawrence; KOOS, Knee Injury and Osteoarthritis Outcome Score; MACI, matrix induced autologous chondrocyte implantation; MRI, magnetic resonance imaging; SMSCs, synovium-derived mesenchymal stromal cells; UC-MSCs, umbilical cord-derived mesenchymal stromal cells; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Arthritis Index.