Table 2.
Studies of human pluripotent stem cell-MSC-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 | 50-150 | CD9, CD63, CD81 | Not mentioned | Dose dependent increase in proliferation, ALP activity and mineral deposition in BM-MSCs. Increased levels of RUNX2, COL1 and ALP. | 5 mm rat (osteopenic) calvarial defect | β-Tricalcium phosphate scaffold | 100, 200 μg/ml | 8 wk- Dose dependent increase in BMD, BV/TV, neovascularization. More OCN, OPN & CD31 expression in 200 μg/ml group | Not mentioned | (Qi et al., 2016) |
| Human | Not mentioned | 30-100 | CD9, CD63, CD81 | Not mentioned | Internalized by HUVECs. Increased expression of BCL2A1, Sphk1, MYC in HUVECs | Steroid induced ONFH in rats | tail vein injection | 1 × 1010/ml or 1 × 1011/ml | 3 wk- Fewer empty lacunae and necrotic medullary hematopoietic and adipose cells, increased trabecular bone structural integrity, higher BV/TV, bone surface area/bone volume, Tb.Th and Tb.N, more vascular branches, increased expression of VEGFR2 & CD31 | PI3k/AKT | (Liu et al., 2017) |
| Human | Not mentioned | 50-150 | CD9, CD63, CD81 | Not mentioned | Dose dependent increase in proliferation and ALP activity in BM-MSCs. Increased levels of PDGFA, FGF1/2, FGFR1, COL1A1 & BCL2L1 | 5 mm rat calvarial defects | β-Tricalcium phosphate scaffold | 5 × 1011 particles/ml or 1 × 1011 particles/ml | 8 wk- Dose-dependent increase in bone regeneration; more tetracycline, alizarin red, calcein and OCN staining | PI3k/AKT signaling increase in PDGFA, FGF1/2, FGFR1, COL1A1, BCL2L1 and decrease in GSK3β, PTEN. | (Zhang et al., 2016) |
BMD: Bone mineral density; PDGF: Platelet derived growth factor; FGF: Fibroblast growth factor; FGFR: FGF receptor; Tb. Th: Trabecular thickness; Tb.N: trabecular number; ONFH: Osteonecrosis femoral head; ALP: Alkaline phosphatase; BM-MSC: Bone marrow derived mesenchymal stromal cell; RUNX: Runt-related transcription factor; COL: Collagen; BV/TV: Bone volume/Total volume; OCN: Osteocalcin; OPN: Osteopontin; HUVECs: Human umbilical vein endothelial cells; VEGFR: Vascular endothelial growth factor receptor; BCL2L1: B-lymphoma-2 like protein-1; AKT: Protein kinase B; PI3K: Phosphoinositide 3-kinase; GSK: Glycogen synthase kinase; PTEN: Phosphatase and tensin homolog.