Table 2.
In vivo efficacy of MSC-EVs in animal cartilage/osteochondral models.
| EV source | Dose/volume | Animal type | Disease model | Molecular mechanisms | Biological Outcomes | Reference |
|---|---|---|---|---|---|---|
| IPFP-MSCs* | 10 μl 1010 particles mL-1 |
Mice | Surgical destabilization of the medial meniscus (DMM) | Inhibition of mTOR | Prevent the cartilage destruction and partially improve the gait abnormality in the DMM mice model | 134 |
| human embryonic stem cell-derived MSCs | 100 µg EVs per 100 µl of injection | Rat | Osteochondral defect model created on thetrochlear grooves of the distal femurs | CD73-mediated adenosine activation of AKT and ERK signallings. | Improve the surface regularity and integration with host cartilages, improve the quality of osteochondral repair | 163 |
| hBMMSCs | 15 μl 500 μg mL-1 in PBS |
Mice | Collagenase VII-induced OA model | MiR-92a-3p directly targets the 3'-UTR of WNT5A mRNA | Inhibit the progression of early OA, prevent the damage to knee articular cartilage | 164 |
| mBMMSCs | 250 ng per 5 µL | Mice | Collagenase VII-induced arthritis model | Re-induce the expression of chondrocyte markers while inhibiting catabolic and inflammatory markers | Higher bone volume (BV/TV parameter); less bone degradation | 165 |
| hBMMSCs | 100 μL of 1011 particles mL-1 | Mice | Mouse model of traumatic OA in a mechanical test device | miR-136-5p target ELF3, downregulate its expression | Higher expression of collagen II and aggrecan inhibits early post-traumatic OA and prevents further damages to the knee cartilage. | 166 |
| mBMMSCs* | 200 μg of EVs 200 in μl PBS | Mice | Lumbar facet joint (LFJ) osteoarthritis model | Suppressing RANKL‐RANK‐TRAF6 Signalling Pathway | Attenuate the articular Cartilage degeneration, promote cartilage and subchondral bone remodeling | 167 |
| hBMMSCs* | 250 ng per 5 µL | Rat | left knee joints of the rats were opened to expose the joints, followed by skin suture | miR-26a-5p specifically target PTGS2 | Alleviate synovial tissue proliferation, reduced inflammatory cells, and attenuated pathological changes of synovial tissues | 168 |
| Synovial MSCs | 100 μL; 1011 EV particles mL-1 | Rat | Transecting the medial collateral ligament and the medial meniscus completely | YAP activation via the alternative Wnt signalling pathway | Slow the progression of early OA and preventedsevere damage to knee articular cartilage | 135 |
| UCMSCs | 100 μL; 1 mg mL-1 | Rat | A drill bit (1.5 mm diameter) was used to make cartilage defects on the distal femurs | UCMSC-EVs contain high content of lncRNA H19 | Promote chondrocyte proliferation and matrix synthesis and inhibit apoptosis in vitro; promote cartilage repair in vivo |
148 |
*represent the EVs are collected from modified MSCs. Abbreviations: murine bone marrow mesenchymal cells (mBMMSCs); infrapatellar fat pad (IPFP) MSCs; human bone MSC (hBMMSC); umbilical cord mesenchymal stem cells (UCMSCs).