Table 1.

Summary of major findings of OA-related studies involving the use of exosomes.

Cells	Source	Extraction	Dose	Delivery Method	Target Cells	Results	Ref
VECs	Conditioned medium	Ultrafiltration	100 μg	Co-incubation for 24 h	Primary chondrocytes	Promoted OA progression by inhibiting chondrocyte autophagy, downregulating p21 expression, and increasing ROS production and apoptosis.	[29]
OA chondrocytes	Culture supernatant	Ultracentrifugation	1 × 106/mL	Co-incubation	Synovial macrophages	Promoted OA progression by stimulating inflammasome activation and upregulating mature IL-1β production in synovial macrophages	[30]
Primary chondrocytes	Conditioned medium	Ultracentrifugation	200 μg/mL	Co-incubation for 48 h Intra-articular injection	Chondrocytes	Prevented OA via the restoration of mitochondrial function and macrophage polarization toward the M2 phenotype	[31]
OA osteoblasts	Conditioned medium	Ultracentrifugation	20 μg/mL	Co-incubation for 14 d	Chondrocytes	Promoted OA progression by suppressing oxygen consumption by chondrocytes via miR-210-5p.	[32]
BM-MSCs	Conditioned medium	Ultracentrifugation	10 μg/mL	Co-incubation for 24 h	Chondrocytes	Promoted proliferation and inhibited apoptosis of chondrocyte via miR-206/GIT1 axis	[33,34]
BM-MSCs	Conditioned medium	Ultracentrifugation	250 ng	Intra-articular injection	Chondrocytes	Prevented OA development by inhibiting the degradation of cartilage and the formation of osteophyte	[35]
BM-MSCs	Conditioned medium	Ultracentrifugation	200 μg/mL	3D printed ECM/GelMA/exosome scaffolds	Osteochondral defect rabbit model	Prevented OA development by facilitating cartilage regeneration and restoring chondrocyte mitochondrial function	[36]
SMSCs	Conditioned medium	Ultracentrifugation	5 μg	Co-incubation for 12 h	Chondrocytes	Prevented the development of OA by facilitating migration, proliferation and ECM secretion and suppressing chondrocyte apoptosis	[37]
SMSCs	Conditioned medium	Ultracentrifugation	1010 particles	Intra-articular injection	DMM mice model	Prevented OA development by enhancing cartilage tissue regeneration via miR-140-5p upregulation of Wnt and YAP	[38]
ESC-MSCs	Conditioned medium	Ultrafiltration	5 μg/mL 100 μg	Co-incubation for 48 h Intra-articular injection	TMJ condylar chondrocytes	Prevented OA development via inflammation attenuation and matrix homeostasis restoration	[39]
ESC-MSCs	Conditioned medium	Ultracentrifugation	881 ng	Intra-articular injection	DMM OA model	Prevented OA development by balancing cartilage ECM synthesis and degradation	[40]
iPSC-MSCs	Conditioned medium	Ultracentrifugation	8 μL 1010/mL	Intra-articular injection	Collagenase-induced OA model	Prevented OA development by promoting migration and proliferation of chondrocytes	[41]
UC-MSCs	Conditioned medium	Ultracentrifugation	10 μg/mL 100 μg	Co-incubation for 72 h Intra-articular injection	Rat cartilage defect model	Mechanical stimulation increased the expression level of LncRNA H19 in exosomes, which promoted chondrocyte proliferation, matrix synthesis, and inhibited apoptosis	[42]
ADSCs	Conditioned medium	Ultracentrifugation	400 µg/mL	Co-incubation for 48 h	Chondrocytes	Prevented OA development by promoting chondrogenesis and suppressing inflammation via upregulating miR-221 and miR-145	[43]
ADSCs	Conditioned medium	Ultracentrifugation	108 particles	Intra-articular injection	DMM and MIA induced OA model	Prevented OA development by inhibiting proteoglycan degradation and cartilage destruction and ameliorating gait abnormality	[44,45]
AFSC	Conditioned medium	Precipitation	30 μg 100 μg	Co-incubation for 72 h Intra-articular injection	MIA-induced OA mice model	Prevent the development of OA by promoting chondrocyte proliferation, cartilage matrix synthesis, and polarizing macrophages to M2 phenotype	[46]
Engineered CAP-Lamp2b exosomes	Conditioned medium	Ultracentrifugation	10 μg 100 μg	Co-incubation for 3 h Intra-articular injection	Chondrocytes DMM OA rat model	Prevented OA development by delivering miR-140 to deep cartilage regions and inhibiting cartilage-degrading proteases	[47]
CPCs	Conditioned medium	Ultracentrifugation	108/mL 8 × 107 particle	Co-incubation for 3 h Intra-articular injection	Chondrocytes	Enhanced articular cartilage repair by stimulating chondrocyte proliferation and migration via upregulating miRNA 221-3p	[48]
Synoviocytes	Conditioned medium	Ultracentrifugation	20 μg/mL	Co-incubation for 24 h	Chondrocytes	Promoted OA progression by inducing apoptosis and cartilage matrix degradation via upregulating miR-142-5p/RUNX2	[49]
Synovial fibroblasts	Patient synovial fluid	Ultracentrifugation	2 × 109/mL 20 μg	Co-incubation for 48 h Intra-articular injection	ACLT  +  MMx OA rat model	Prevented OA development by suppressing chondrocyte apoptosis, constraining inflammation, and cartilage degeneration	[50]
PRP	PRP	exoEasy Maxi Kit	50 μg/mL 100 μg/mL	Co-incubation for 24 h Intra-articular injection	Chondrocytes	Prevented OA development by facilitating proliferation and reducing apoptosis of chondrocyte via Wnt/β-catenin	[17]
CPRP	Whole blood	Ultracentrifugation	1.42 × 109 particles	Co-incubation for 48 h	OA chondrocytes	Prevented OA development by inducing chondrogenic gene expression changes and preventing proinflammatory cytokine release	[51]
IPFP	IPFP	Ultracentrifugation	10 μL 1010/mL	Intra-articular injection	DMM mice model	Prevented OA development by alleviating articular cartilage damage via miR-100-5p downregulation of mTOR	[44]
Tenocyte	Conditioned medium	Ultracentrifugation	486.3 μg/mL	Co-incubation for 48 h	Tendon stem cells	Promoted tendon healing by regulating tendon ECM metabolism and inducing the tenogenic differentiation of MSCs via upregulating transforming growth factor-beta	[52,53]
Periodontal ligament cells	PureExo® exosome isolation kit	Precipitation	5 μg/mL	Co-incubation for 48 h	Macrophage	Regulated macrophage function and maintained inflammation homeostasis by suppressing IL-1β via inhibiting NF-κB signaling pathway	[54]
LPS-pretreated PDLFs	Conditioned medium	Ultracentrifugation	100 μg/mL	Co-incubation for 48 h	Osteoblast	Prevented bone remodeling by inducing inflammation and inhibiting osteogenic activity of osteoblasts, promoting macrophage polarization toward M1 via YAP	[55,56]

VECs: vascular endothelial cell; BM-MSCs: bone marrow mesenchymal stem cells; ESC-MSCs: embryonic stem cell-derived MSCs; iPSC-MSCs: induced pluripotent stem cells-derived MSCs; UC-MSCs: umbilical cord mesenchymal stem cells; CPCs: chondrogenic progenitor cells; DMM: destabilization of the medial meniscus; ACLT + MMx: anterior cruciate ligament and resecting the medial menisci; PRP: platelet-rich plasma; CPRP: citrate-anticoagulated platelet-rich plasma; SMSCs: synovial mesenchymal stem cells; IPFP: infrapatellar fat pad; AFSC: amniotic fluid stem cells; ADSCs: adipose-derived stem cells; MIA: monosodium iodoacetate; PDLSCs: periodontal ligament-derived stem cells; PDLFs: periodontal ligament fibroblasts.