Table 2. Details of preclinical articles identified in present review.
| Author | Year | Animal type | Stem cell type | Hydrogel type | Study design | Results |
|---|---|---|---|---|---|---|
| Jia et al. (68) | 2019 | Rabbits; Chondral defect | SF-MSCs; 1×106/mL | Chitosan | (I) SF-MSCs + hydrogel; (II) hydrogel; (III) control. 6 animals for each group. Experimental time: 4, 8 and 12 weeks |
Hydrogel/SF-MSCs was superior to using the hydrogel scaffold only and the untreated control based on gross appearance and histological grading and evaluation |
| Wu et al. (63) | 2019 | Minipigs; Osteochondral defect | HUC-MSCs; 5×106 cells | HA | (I) HUC-MSCs + HA; (II) untreated. 2 animals for each group. Experimental time: 12 weeks |
Cartilage regeneration using a mixture of HUC-MSCs and HA in a large animal model may be an effective treatment for OA |
| Park et al. (67) | 2019 | Rats; Osteochondral defects | MSCs | HA | (I) Chondro-MSCs + HA; (II) Undiff-MSCs + HA; (III) HA; (IV) untreated. 20 animals for each group. Experimental time: 8 and 16 weeks |
Transplanting undiff-MSCs resulted in overall superior cartilage repair as compared with chondro-MSCs, HA alone, or no treatment |
| Pascual-Garrido (66) | 2019 | Rabbits; Chondral defect | BMSCs | Novel photopolymerizable hydrogel | (I) hydrogel + BMSCs; (II) hydrogel; (III) control. 5 animals for each group. Experimental time: 6 months |
Novel photopolymerize hydrogel is able to provide chondrogenic cues for cartilage repair in a rabbit model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel |
| Critchley et al. (35) | 2019 | Rabbits; Chondral defect | BMSCs; 2×107 cells/mL | Alginate | (I) hydrogel + BMSCs; (II) control. 6 animals for each group. Experimental time: 3 months |
Cartilage template, engineered using BMSCs, can enhance the regeneration of defects and promote the development of a more mechanically functional repair tissue |
| Li et al. (71) | 2018 | Rats; Chondral defect | AFF- MSCs; 1×106/mL | Polypegda/HA | (I) AFF-MSCs + hydrogel; (II) hydrogel; (III) control. 10 animals for each group. Experimental time: 4 and 8 weeks |
AFF-MSCs/hydrogel composite significantly repair full-thickness cartilage defects generated in a rat model; smooth cartilage was formed with evidence of hyaline cartilage formation |
| Choi et al. (74) | 2018 | Rabbits; Osteochondral defect | BMSCs; 2×106 cells | HA | 4 group: 3/group. (I) HA + BMSCs + Res; (II) HA + BMSCs; (III) HA; (IV) control. 3 animals for each group. Experimental time: 8 weeks |
The cartilage regeneration potential of Res-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in Rsv-treated MSCs compared with untreated MSCs |
| Uto et al. (69) | 2018 | Pigs; Osteochondral defect | iPSCs | Beta-TCP | (I) beta-TCP + iPSCs; (II) beta-TCP + MSCs; (III) beta-TCP. 2 animals for each group. Experimental time: 4 and 8 weeks |
iPSCs transplanted into osteochondral replacement model, cartilage regeneration was observed without tumor formation |
| Kim et al. (82) | 2012 | Rabbits; Osteochondral defect | BMSCs; 106 cells | HA | (I) MSCs + HA + 2 HA inj; (II) MSCs + HA + 1 HA inj; (III) MSCs + HA; (IV) MSCs; (V) HA; (VI) No treatment. 3 animals for each group. Experimental time: 7 weeks |
Significant improvements in osteochondral defect healing at macroscopic and histological evaluation in all treatment groups compared with untreated defects; at histology, MSCs + HA + 2 HA inj showed better results than other groups |
| Mcilwraith et al. (84) | 2011 | Horses; Osteochondral defect | BMSCs; 2×106 cells | HA | (I) MFX + HA + MSCs; (II) MFX + HA. 5 animals for each group. Experimental time: 6 and 12 months |
No difference in clinical and histological analysis, but significant increase in repair tissue firmness and better repair tissue quality at arthroscopic and macroscopic analysis in MSCs group with greater levels of aggrecan than in HA alone group |
| Saw et al. (85) | 2009 | Goats; Osteochondral defect | MSCs; 220×106 cells | HA | (I) MFX + 3 HA + MSCs inj; (II) MFX + 3 HA inj; (III) No treatment. 5 animals for each group. Experimental time: 24 weeks |
Better cartilage repair in MSCs group at histology, with hyaline cartilage regeneration |
| Lee et al. (86) | 2007 | Minipigs; Osteochondral defect | BMSCs; 7×106 cells | HA | (I) MSCs + HA; (II) HA; (III) Saline. 9 animals for each group. Experimental time: 6 and 12 weeks |
Improvement in cartilage healing at histologic and macroscopic analysis at both 6 and 12 weeks in MSCs + HA group compared with controls |
| Lv et al. (70) | 2018 | Sheep; OA | AD-MSCs; 1×107 cells & 5×107 cells | HA | (I) high dose AD-MSCs + HA; (II) low dose AD-MSCs + HA; (III) SVF; (IV) HA; (V) Saline. 6 animals for each group. Experimental time: 12 and 15 weeks |
Better results in AD-MSCs/HA than SVF/HA in blocking OA progression and promoting cartilage regeneration |
| Feng et al. (72) | 2018 | Sheep; OA | AD-MSCs; 1×107 cells & 5×107 cells | HA | (I) High dosage AD-MSCs + HA; (II) low dosage AD-MSCs + HA; (III) HA; (IV) saline. 7 animals for each group. Experimental time: 14 weeks |
Typical articular cartilage feature in both AD-MSCs groups and presence of AD-MSCs at synovium at 14 weeks at MRI; lower inflammatory factors from synovial fluid of AD-MSCs groups than HA alone |
| Desando et al. (73) | 2018 | Rabbits; OA | BMSCs | HA | (I) BMSCs + saline; (II) BMSCs + HA; (III) BMC + saline; (IV) BMC + HA; (V) HA. 12 animals for each group. Experimental time: 8 weeks |
Joint repair evidence in all treatments, superior results for BMC-HA than other groups; BMSCs migrate to the meniscus while BMC in cartilage, but HA favor cells migration to cartilage |
| Chiang et al. (76) | 2016 | Rabbits; OA | BMSCs (106 cells) | HA | (I) MSCs + HA; (II) HA; (III) Sham; (IV) Untreated. 18 animals for each group. Experimental time: 6 and 12 weeks |
Less cartilage loss and surface abrasion with better histological scores and cartilage content in MSCs group compared with HA alone; engraftment of allogenic MSCs were evident in surface cartilage |
| Suhaeb et al. (79) | 2012 | Rat; OA | BMSCs; 3–5×106 cells | HA | (I) BMSCs + HA; (II) BMSCs; (III) HA. 7 animals for each group. Experimental time: 6 weeks |
Better results with HA and BMSCs alone in counteracting OA progression with respect to their combination |
| Sato et al. (80) | 2012 | Pigs; OA | MSCs; 7×106 cells | HA | (I) MSCs + HA; (II) MSCs + saline; (III) HA; (IV) Saline. 15 animals for each group. Experimental time: 5 weeks |
Histological partial defect repair only in MSCs + HA group at 5 weeks with an increase in type-II collagen content and low levels of MMP-13 |
| Mokbel et al. (83) | 2011 | Donkeys; OA | BMSCs; 1.8–2.3×106 cells | HA | (I) BMSCs + HA; (II) HA alone. 9 animals for each group. Experimental time: 1, 2, 6 months |
Reparative effect of clinical and radiological evaluation in BMSCs + HA group compared with the control; BMSCs integrated with healthy cartilage in the superficial and inner part |
| Murphy et al. (87) | 2003 | Goats; OA | BMSCs; 10×106 cells | HA | (I) HA + BMSCs; (II) HA. 6 animals for each group. Experimental time: 12 and 26 weeks |
No adverse events; stimulation of the regeneration of meniscal tissue and delay of OA progression in BMSCs group |
| Kim et al. (75) | 2016 | Rat; OA | MSCs; 1.5×106 cells | SAP-SP hydrogel | (I) SAP-0.5SP; (II) SAP-SP; (III) SAP-2SP; (IV) SAP-SP-MSCs; (V) control. 7 animals for each group. Experimental time: 6 weeks |
Markedly improved cartilage regeneration in the SAP-SP group showing recruitment of MSCs in the defect. SAP-SP restore articular joint function without cell transplantation |
| Kim et al. (77) | 2014 | Rat; OA | BMSCs (106 cells) | SAP hydrogel | (I) SAP-BMSCs; (II) SAP; (III) BMSCs; (IV) control. 6 animals for each group. Experimental time: 6 weeks |
Evidence of chondroprotection at histological view and decrease of inflammation and apoptosis biomarkers in SAP + BMSCs group; increased BMD in SAP+ BMSCs groups relative to the controls |
MSCs, mesenchymal stem cells; BMSCs, bone marrow-derived MSCs; SF-MSCs, synovial fluid-derived MSCs; HUC-MSCs, human umbilical cord-derived MSCs; OA, osteoarthritis; HA, hyaluronic acid; AFF-MSCs, arthroscopic flushing fluid MSCs; Res, resveratrol; iPSCs, induced pluripotent stem cells; beta-TCP, beta-tricalcium phosphate; inj, injection; MFX, microfracture; AD-MSCs, adipose-derived MSCs; SVF, stromal vascular fraction; BMC, bone marrow concentrate; SAP, self-assembled peptide; SP, substance P.