Table 3.
Studies of uMSC-derived EVs for promoting bone regeneration.
EV cell origin |
EV size (nm) |
Content profile |
In vitro effects |
In vivo |
Pathway(s) involved | Ref | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Species | Passage | Markers | miRNA | Model | Delivery mechanism | Amount of EVs delivered | In vivo effects | ||||
Human | Not mentioned | 30-100 | CD9, CD63, CD81 | Not mentioned | None | SD rat femoral fracture | HyStem®-Heparin hydrogel | 100 μg | 3 wk- Increased fracture healing in EV group as compared to control groups; higher expression of β-catenin, Wnt3a, COL1, OPN and RUNX2 | β-catenin and Wnt 3a | (Zhou et al., 2019) |
Human | 2nd to 5th | 100 | CD9, CD63, CD81 | Not mentioned | Internalization by HUVECs. Increased proliferation, migration and tube formation by HUVECs with increased expression of VEGF and HIFα1. No effect on osteoblast proliferation or differentiation. | Rat femoral fracture | Hystem®-Heparin hydrogel | 100 μg/ml | 4 wk-Larger callus volume, increased bone mineral density, BV and BV/TV; increased CD31+ blood vessels, enhanced maximum load at failure and bending stiffness | HIF1α | (Zhang et al., 2019) |
HIF: Hypoxia inducible factor; SD: Sprague Dawley; COL: Collagen; OPN: Osteopontin; RUNX: Runt-related transcription factor; HUVECs: Human umbilical vein endothelial cells; VEGF: Vascular endothelial growth factor; BV: Bone volume; TV: total volume; EV: Extracellular vesicle.