Table 3 Summary of knee OA models characteristics
Ref. | Producing cells | Animal model | Disease model | Administration route | Treatment | Outcomes | ||
|---|---|---|---|---|---|---|---|---|
Strain/Sp | Sex | Age | ||||||
[25] | SMSCs (human) | C57BL/6 mouse | Male | 10 weeks | DMM (ACLT + medial meniscectomy) | Intraarticular | 109 EVs/10 µl Twice a week/6 weeks (3 days after surgery) No further follow-up | Reduced OARSI score Increased ACAN, COL2; reduced ADAMTS5 [IF] |
[17]†| ADSCs (human) | C57BL/6 mouse | Male | 8 weeks | Collagenase-induced OA | Intraarticular | 109 CMD4 EVs/8 µL 8 days after CIOA Follow-up: 20 days | Reduced OARSI score* Reduced macroscopic chondropathy score |
[54] | BMSCs (mouse) | C57BL/6 mouse | Male | 8 weeks | DMM (ACLT) | Intraarticular | 108 EVs/10 µl Once a week/4 weeks (2 weeks after surgery) No further follow-up | Reduced OARSI score Reduced osteophyte score Reduced MMP13 [IHQ] |
[31]†| ADSCs (human) | C57BL/6 mouse | Male | 10 weeks | DMM (Medial MTL transection) | Intraarticular | 108 EVs/6 µl PBS Once a week/6 weeks (5 weeks after surgery) No further follow-up | Reduced OARSI Score Reduced MMP13 [IHQ] |
[32] | ADSCs (mouse) | C57BL/6 mouse | Male | - | DMM (ACLT) | Intraarticular | 109 EVs/mL Twice a week/4 weeks No further follow-up | Reduced Mankin score* No difference in ACAN; increased COL2 [IHQ] |
[55] | UCMSCs (human) | C57BL/6 mouse | Male | 12 weeks | DMM (Medial MTL transection) | Intraarticular | 109 EVs/5 µL PBS 0, 2 and 4 weeks after surgery Follow-up: 4 weeks | Reduced OARSI/Mankin Score More cartilage in tibial plateau Reduced MMP13, ADAMTS5 [IF] |
[58] | UCMSCs (human) | C57BL/6 mouse | Male | 8 weeks | DMM (ACLT + medial meniscectomy) Exercise 1 h/day | Intraarticular | 109 EVs/10 µL PBS Twice a week/6 weeks No further follow-up | Reduced OARSI score Reduced osteophyte formation Increased COL2, ACAN; reduced ADAMTS5/MMP13 [IF] Reduced IL-1β; no changes in TNF-α [ELISA] |
[51] | ADSCs (human) | NOD mouse | - | - | Osteochondral defect | Intraarticular | 2 µl of EVs (320X) 1 week after surgery Follow-up: 4 weeks | Increased cartilage repair score Increased proteoglycans; Increased COL2; reduced COL1 [IF] |
[56] | UCMSCs (human) | SD Rat | Male | 8 weeks | DMM (ACLT) | Intraarticular | 200 µl EVs (30 µg) Once a week/4 weeks (4 weeks after surgery) Follow-up: 1 week | Reduced OARSI score* Increased BVF Reduced MMP13, ADAMTS5 [IHQ] |
[37] | UCMSCs (human) | SD Rat | Male | 8 weeks | Osteochondral defect | Implantation into cartilage defect | Gel with 109 EVs/mL (during surgery) Follow-up: 12 weeks | Increased ICRS histological score* and macroscopic score |
[49] | ADSCs (human) | SD Rat | Male | 10 weeks | Monoiodoacetate | Intraarticular | CD10High sEVs (secreted by 106 cells)/50 µl EuroCollins 4 days after MIA Follow-up: 4 days | Reduced histological score* Increased PRG4 superficial expression [IF] |
[57] | UCMSCs (human) | SD Rat | Male | 6–8 weeks | DMM (ACLT) | Intraarticular | 80 µg/mL Once a week/4–8 weeks No further follow-up | Reduced Mankin score Reduced macroscopic chondropathy score Reduced MMP13 [IHQ] |
[29] | BMSCs (rat) | SD Rat | Male | 10 weeks | Osteochondral defect | Implantation into cartilage defect | Gel w/125 µg/kg (sEVs/BW) (100 µL) (during surgery) Follow-up: 4–8 weeks | Increased cartilage repair* Increased ICRS macroscopic score No changes in MMP13/COL2 [IHQ] |
[50] | SFMSCs (rat) | SD Rat | Male | 10 weeks | DMM (ACLT + transverse ligament transection) | Intraarticular | 50 µg EVs/100 µL PBS Once a week/10 weeks (8 weeks after surgery) No further follow-up | Reduced OARSI score Increased COL2; reduced MMP13 [IHQ] Reduced serum inflammatory cytokines [ELISA] |
[35] | UCMSCs (human) | SD Rat | - | 8 weeks | Monoiodoacetate | Intraarticular | 108 EVs/10 µL PBS Once a week/4 weeks (1 week after MIA) No further follow-up | Reduced Mankin score* No changes in articular space width No changes in subchondral bone (BVF) |
[41] | SMSCs (human) | SD Rat | Male | 10 weeks | DMM (ACLT + MCL transection) | Intraarticular | 3 × 109 EVs/30 µL PBS Once a week/3 weeks (1 week after surgery) Follow-up: 1 week | Reduced Mankin score* Reduced inflammatory cytokines [ELISA] Reduced apoptosis |
[38] | BMSCs (human) | SD Rat | Male | 10 weeks | Collagenase-induced OA | Intraarticular | 400 µg EVs/mL 1 week after CIOA Follow-up: 6 weeks | Reduced OARSI/Mankin score* |
[26] | BMSCs (rat) | SD Rat | Female | 7–8 weeks | DMM (ACLT + medial meniscectomy) | Intraarticular | 200 µg EVs/200 µL PBS 4 weeks after surgery Follow-up: 4 weeks | Reduced OARSI score Reduced osteophyte score Increased COL2 [IHQ/WB] |
[42] | UCMSCs (human) | SD Rat | Male | 8 weeks | DMM (ACLT) | Intraarticular | 30 µg EVs/200 µL PBS Once a week/4 weeks (1 week after surgery) Follow-up: 4 weeks | Reduced OARSI score* Increased COL2 [IHQ] |
[53] | SMSCs (human) | SD Rat | Male | 12 weeks | DMM (ACLT + medial meniscectomy) | Intraarticular | 2 × 1010 EVs/200 µl in hydrogel Every 4 weeks (x6) No further follow-up | Regenerated tissue with disorganized arrangement and poor in proteoglycans |
[31]†| ADSCs (human) | SD Rat | Male | 8 weeks | Monoiodoacetate | Intraarticular | 108 EVs/30 µl PBS Subacute: Once a week/21 days (1 week after surgery) Chronic: Twice a week/40 days (2 weeks after surgery) No further follow-up | Reduced Modified Mankin score (modest reduction in the chronic model) |
[43] | ADSCs (rat) | SD Rat | Male | 8 weeks | Osteochondral defect | Implantation into cartilage defect | 7.5 × 109 EVs/10 µl gel (during surgery) Follow-up: 4–8 weeks | Increased ICRS score* Increased collagen organization Reduced apoptosis Increased BVF and BMD |
[27] | BMSCs (human) | SD Rat | Female | 4 weeks | DMM (ACLT + medial meniscectomy) | Intraarticular | 50–100 µg EVs/100 µL PBS 4 weeks after surgery Follow-up: 4 weeks | Reduced Modified OARSI score* Increased COL2 [IHQ] |
[59] | BMSCs (rabbit) | Wistar Rat | Male | 8 weeks | Monoiodoacetate | Intraarticular | 50 µg EVs/50 µl PBS Once a week/4 weeks (3 weeks after MIA) Follow-up: 8 weeks | Increased stride and step length, reduced toe-out angle and gait irregularity Reduced Mankin score* Reduced radiological score Increased COL2 [IHQ] |
[47] | BMSCs (rabbit) | Wistar Rat | Male | 8 weeks | Monoiodoacetate | Intraarticular | 100 µg EVs/50 µl PBS Once a week/4 weeks (3 weeks after surgery) Follow-up: 12 weeks | Reduced irregularity in gait Reduced histological score* (2D only) Reduced radiological score (2D only) |
[52] | BMSCs (human) | Wistar-Han Rat | Male | 24 weeks | Groove surgery + metabolic dysregulation (Metabolic OA) | Intraarticular | 7.77 × 107 EVs/25 µl PBS Every 5 days/20 days (x5) (8 days after surgery) Follow-up: 8 weeks | No changes in pain No changes in histology No changes in osteophytes/ subchondral bone Reduced systemic inflammation [ELISA] |
[48] | UCMSCs (human) | New Zealand Rabbit | - | - | Osteochondral defect | Intraarticular (EVs) and implantation into cartilage defect (S) | 5 µg EVs/200 µl PBS Once a week/5 weeks (3 weeks after surgery) Follow-up: 2–5 months | Increased histomorphology score* (with fibrillation and other alterations) ↑ ICRS macroscopical score No changes in WORMS Increased BVF (in combination with scaffold) |
[44] | BMSCs (human) | New Zealand Rabbit | Male | 26 weeks | Osteochondral defect | Intraarticular | 3–15 × 109 EVs/300 µl Once a week/4 weeks (1 week after surgery) No further follow-up | Increased ICRS score* Unsmooth surface Safranin O staining intensity not recovered |