Osteoarthritis (OA) is a prevalent and debilitating age-related joint disease characterized by articular cartilage degeneration, synovial membrane inflammation, osteophyte formation, as well as subchondral bone sclerosis. OA drugs at present are mainly palliative and do not halt or reverse disease progression. Currently, no disease-modifying OA drugs (DMOADs) are available and total joint arthroplasty remains a last resort. Exosomes are a type of extracellular vesicles (EVs) with a diameter ranging between 30 and 150 nm, and a density of 1.13–1.19 g/mL [13]. These extracellular membrane-bound vesicles are able to work as cell-specific cargoes, which contain complex signaling molecules such as lipids, proteins, metabolites, nucleic acids, and cytosolic and cell-surface proteins [13].
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.
This entry is adapted from the peer-reviewed paper 10.3390/bioengineering9030099