Table 4.
Studies of human adipose stem cell and perivascular stem cell -derived EVs for promoting bone regeneration.
| EV cell origin |
EV size (nm) | Content profile |
In vitro effects |
In vivo |
Pathway(s) involved | Ref | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Species | Cell type | Passage | Markers | miRNA | Model | Delivery mechanism | Amount of EVs delivered | In vivo effects | ||||
| Human | Adipose stem cells | Not mentioned | 33-17 | CD9, CD63 | not mentioned | Internalized by BM-MSCs. Increased ALP activity and mineralization with increased RUNX2, COL1A1 and ALP expression (when cultured in OM) | 4 mm murine calvarial defect | PLGA-pDA scaffold | 1 μg/ml | 6 wk- PLGA/pDA-EV group showed some bone formation along the margins of the defect, increased mature collagen deposition, and increased immunostaining for RUNX2 & OCN. Other groups showed no bone and/or fibrotic tissue formation | Not mentioned | (Li et al., 2018) |
| Human | Adipose stem cell | 4th to 6th | 100-800 | CD9, CD81 | miR-21, 10a, 10b, 199b, let-7f | Increased viability, calcium deposition and expression of ALP, OCN & COL1 gene expression in MG63 cells | SQ nude mice model | Biotin doped polypyrrole coated titanium substrates | 10 μg/ml | 4 wk- More OCN positive cells in EV group as compared to control groups | Not mentioned | (Chen et al., 2019a) |
| Human | Adipose derived-PSCs | 3rd to 9th | 100 | Not mentioned | Not mentioned | Internalized by BM-MSCs. Increased ALP Activity. | 1.8 mm murine calvarial defect | Percutaneous injection over the defect region | 1 or 2.5 mg | 4 wk- Increased osteoblastic proliferation at the bone defect edge; significant narrowing of the gap between bony fronts and an enrichment of OCN+ cells at the leading edges of the defect site. | IGSF8 or PTGFRN KD nullified the pro-migratory effects of PSC-EVs | (Xu et al., 2019) |
pDA: polydopamine; PSC: Perivascular stem cells; KD: Knock down; IGSF: Immunoglobulin superfamily; PTGFRN: Prostaglandin F2 receptor negative regulator; BM-MSC: Bone marrow derived mesenchymal stromal cell; ALP: Alkaline phosphatase; COL: collagen; OM: Osteogenic medium; OCN: Osteocalcin; PLGA: Poly lactic-co-glycolic acid; RUNX: Runt-related transcription factor; EV: Extracellular vesicle; SQ: Subcutaneous.