Table 4.
Effect of mesenchymal stem/stromal cell extracellular vesicles on angiogenesis in animal models
| EV source | Animal/wound model | EV dose | EV effect | Signalling pathway | References |
|---|---|---|---|---|---|
| P-MSCs | Mice (hind limb ischemia) |
1 × 10¹¹ particles/ml, single injection |
↑ volume of blood vessels improvement of blood flow |
- | Hao et al. 2022 [41] |
| UC-MSCs | Rats (10 mm full-thickness excisional skin wounds) | 100 µg protein, single topical application |
↑ microvessel density increase in VEGF and TGFβ-1 expression |
- | Yang et al. [30] |
| BM-MSCs |
Diabetic mice (8 mm full-thickness excisional skin wounds) Rats (12 mm full-thickness excisional skin wounds) |
50 µg protein, single dose on the third day after procedure | ↑ in the number of axial vessels | - | Born et al. 2022 [32] |
| P-MSCs | Mice (corneal alkaline burn) | 33,33 µg protein/µl, three times a day/3 weeks |
inhibition of angiogenesis ↓ in VEGF-α, MMP2 and MMP9 levels reduction in vessel density |
- | Tao et al. 2019 [33] |
| AD-MSCs |
Minipig (full-thickness excisional skin wound, 30 mm x 30 mm) Mice (dermal filler model) |
Minipigs: 4.0 × 10¹⁰ particles/ml, 3 times a week Mice:1.4 × 10⁹ particles/ml, given once |
↑ vascularization | - | Lee et al. 2023 [29] |
| WJ-MSCs | Mice (full-thickness incisional skin wounds, ulceration created) | 1 × 10⁸ EVs/ mouse, daily for three days after the procedure |
↑ expression of VEGF, Ang-1, Ang-2 ↑ in the number of axial vessels |
- | Kim et al. 2023 [31] |
| AD-MSCs | Diabetic rats (10 mm full-thickness excisional skin wounds) | 100 µg protein/ml, single application | ↑ number of CD31-positive cells | PI3K-AKT-mTOR-HIF-1a | Liu et al. 2021 [35] |
| UC-MSCs | Rats (8 mm full-thickness excisional skin wounds) | ND | ↑ in the number of blood vessels | - | Tang et al. 2023 [36] |
| UC-MSCs | Mice (6 mm full-thickness excisional skin wounds) | 7 × 1010 particles/ml, single application | improved tissue perfusion and vessel density | - | Lu et al. 2024 [45] |
| FS-MSCs | Diabetic mice (6 mm full-thickness excisional skin wounds) | 200 µg protein/mice, daily in the form of a solution |
↑ number of CD31-positive cells restoration of the structural and functional network of blood vessels |
- | Xu et al. 2024 [44] |
P-MSCs Placental Mesenchymal Stem/Stromal Cells, UC-MSCs Umbilical Cord Mesenchymal Stem/Stromal Cells, BM-MSCs Bone Marrow Mesenchymal Stem/Stromal Cells, VEGF Vascular Endothelial Growth Factor; TGFβ-1 Transforming Growth Factor Beta 1, MMP2 Matrix Metalloproteinases 2, MMP9 Matrix Metalloproteinases 9, CD31 vascular endothelial cells marker; full-thickness excisional skin wound - damage affecting the entire thickness of the skin – from the epidermis, through the entire layer of the dermis, to the border with the subcutaneous tissue with causing a loss of tissue volume; full-thickness incisional skin wounds - an incisional wound is a type of full thickness wound that is created by a surgical blade or another sharp instrument during a surgical procedure, such as a scalpel, which cuts or parts the tissue without causing a loss of tissue volume, ND no data, ↑ increased, ↓ decreased