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. 2021 May 17;14:101093. doi: 10.1016/j.bonr.2021.101093

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.

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