Table 4.

Different sources of sEVs and their application in cartilage regeneration

Source	Cell experiment	Animal experiment	Utilization	Roles of sEVs in tissue regeneration	Potential mechanisms
Embryonic stem cell-derived MSCs	Chondrocytes; 5 µg/ml	Rat; dose: 2 mg/ml	Osteoarthritis treatment [232]	Promote temporomandibular joint repair and regeneration [232]	Ameliorate inflammation and suppress apoptosis and matrix degradation to achieve overall joint homeostasis [232]
MSCs	Primary chondrocytes; 10 µg/ml	–	Osteoarthritis treatment [233]	Promote chondrocytes proliferation [233]	Activation of miR-206/GIT1 axis [233]
Primary MSCs	Primary chondrocytes; 50 µg/ml	–	Osteoarthritis treatment [234]	Promote chondrogenesis and enhance chondrocytes proliferation [234]	Inhibit HDAC2/8 expression and promote cartilage matrix expression [234]
Embryonic stem cell-derived MSCs	-	Rat model; dose: 1 mg/ml	Cartilage regeneration [235]	Promote cartilage and subchondral bone repair [235]	–
Embryonic stem cell-derived MSCs	Primary chondrocytes; 0.1, 0.5 and 1.0 µg/ml	Rat model; dose: 1 mg/ml	Cartilage regeneration [236]	Promote chondrocytes proliferation and ameliorate inflammation [236]	Coordinated mobilization of multiple cell types and activation of several cellular processes [236]
MSCs	HUVECs; 100 µg/ml	–	Regeneration [237]	Promote angiogenesis [237]	Mediate stem cell-endothelial cell crosstalk [237]
Serum	MSCs, chondrocytes	–	Cartilage regeneration [238]	Promote MSCs towards chondrogenic differentiation [238]	Deliver sEVs-derived miR-140 to MSCs [238]

– No data. SEVs small extracellular vesicles, MSCs mesenchymal stem cells, HDAC2 recombinant histone deacetylase 2, HUVECs human umbilical vein endothelial cells