Table 1 Modification of exosomes for improving osteogenic therapy potential
From: Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration
Modification | Source | Model and time | Dose and route | Molecular mechanism | References |
|---|---|---|---|---|---|
Hypoxic preconditioning | SHEDs | Rat calvarial defects model, 4 and 8 weeks | NA, defect sites injection | Focal adhesion, thyroid hormone synthesis and VEGF signaling pathway ↑ | [50] |
hucMSCs | Mice bone fracture model, 7 days | 200 μg, fracture sites injection | miR-126 expression ↑; SPRED1/Ras/Erk signaling pathway ↑ | [51] | |
BMSCs | Rat osteoarthritis model, 8 weeks | 100 μg, articular cavity injection | hsa-miR-181c-5p, hsa-miR-18a-3p, hsa-miR-376a-5p, and hsa-miR-337-5p expression ↓ | [65] | |
hPDLCs | NA | NA | Rab11a and Rab27a expression ↓ | [66] | |
TNF-α | hASCs | NA | NA | Wnt-3a content ↑ | [72] |
IL-1β | BMSCs | NA | NA | NRF2 signaling pathway ↓ | [73] |
TGF-β1 | BMSCs | Rat osteoarthritis model, NA | 1 × 1010, articular cavity injection | miR-135b expression ↑ | [71] |
Kartogenin | hucMSCs | Rabbit cartilage defects model, 4 weeks | 1.0 × 107 cells/mL, defect sites injection | miR-381-3p expression ↑ | [77] |
mBMSCs | Rat osteoarthritis model, 4, 6 and 8 weeks | NA, articular cavity injection | Chondral matrix regeneration ↑ | [78] | |
Curcumin | BMSCs | Mice osteoarthritis model, NA | NA, articular cavity injection | miR-143 and miR-124 expression ↑ | [79] |
Endogenous cargo loading | miR-375-overexpressing hASCs | Rat calvarial defects model, 3 days, 2, 4 and 8 weeks | 50 μg/mL, defect sites injection | IGFBP3 ↓ | [83] |
miR-181b-overexpressing BMSCs | Rat femoral defects model, 3 months | NA, defect sites injection | Macrophage M2 polarization ↑; PRKCD ↓ | [84] | |
miR-140-5p-overexpressing synovial mesenchymal stem cells | Rat osteoarthritis model, 12 weeks | 1010, articular cavity injection | YAP ↑ | [85] | |
BMP2-overexpressing BMSCs | Rat calvarial bone defects model, 4, 8 and 12 weeks | 5 × 108, defect sites injection | Osteoinductive growth factors (BMP2, BMP9) and transcription factors (RUNX2, OSX) ↑ | [86] | |
BMP2-overexpressing BMSCs | Mice femoral defects model, 15 and 30 days | 50 μg, defect sites injection | BMP2/Smad signaling pathway ↑ | [87] | |
BMSC-ExosMU | Rabbit steroid-induced avascular necrosis of femoral head model, 6 weeks | 80 μg/mL, necrosis region injection | Osteocalcin ↑; alkaline phosphatase ↑ | [88] | |
Loading BMP2 | BMSCs | Mice muscle pocket model, 4 weeks | 150 ng, inserting into the pocket | BMP2, RUNX2 expression ↑ | [91] |
Loading VEGF | ATDC5 | Rat segmental defects model, 6 weeks and 12 weeks | 10 μg, implantation | Alkaline phosphatase ↑; COL1A1 ↑ | [92] |
Aptamer | bone marrow stromal cells | Mice postmenopausal osteoporosis model, 2 months | 100 μg, intravenous injection | miR-26a expression ↑ | [93] |
CXCR4 | NIH-3T3 cells | Mice age-related osteoporosis model, 8 weeks | 100 μL, tail vein injection | miR-188 expression ↓ | [94] |