Table 5.
Extracellular vesicles derived from stem cells promote angiogenesis in other ischemic diseases
| EVs source | EVs type | EVs isolation | Experimental model (target cells/animal models) | Functional cargo | Molecules/pathways activated | Key functions/downstream genes | Reference |
|---|---|---|---|---|---|---|---|
| iMSCs | Exosomes |
Differential centrifugation 0.22-μm pore membrane filtration 30% sucrose/D2O cushion purification Ultracentrifugation |
In vitro (HUVECs) In vivo (mice/hindlimb ischemia model) |
/ | / | HIF-1α, TGF-β, VEGFA1, VEGFA2, angiogenin, bFGF, KDR, bFGFR, and VEGF↑ | Hu et al. [121] |
| PMSCs | Exosomes |
Differential centrifugation Ultracentrifugation |
In vitro (HUVECs) In vivo (mice/hindlimb ischemia model) |
miR-126, VEGF | PI3K/AKT signaling pathway | miR-126↑→PIK3R2↓ pAKT↑ | Du et al. [122] |
| EPCs | MVs | Ultracentrifugation | In vivo (SCID mice/hindlimb ischemia model) | miR-126, miR-296 | / | VEGF↑ | Ranghino et al. [123] |
| CD34+ stem cells | Exosomes | Ultracentrifugation |
In vitro (HUVECs) In vivo (immunocompromised BalbC mice/hindlimb ischemia model) |
miR-126-3p | / | VEGF, angiogenin1, and MMP-9↑ | Mathiyalagan et al. [124] |
| BM-MSCs | Size is between in exosomes and MVs |
Differential centrifugation Ultracentrifugation Density gradient ultracentrifugation 0.45-μm pore membrane filtration |
In vivo (female MC57BL/6 mice/hindlimb ischemia model) | miR-210-3p | / | VEGFR1, VEGFR2, and VEGF↑ | Gangadaran et al. [125] |
| ADSCs | Exosomes | ExoQuick-TC reagent | In vivo (male C57BL/6 J mice/skin flap model) | IL-6 | phosphorylation of STAT3 | Exosomes treatments led to significantly increased flap survival and capillary density compared with I/R on postoperative day 5 | Pu et al. [126] |
| ADSCs | Exosomes |
Differential centrifugation 0.22-μm pore membrane filtration Ultracentrifugation |
In vitro (HUVECs) In vivo (male Sprague-Dawley rats/skin flap model) |
/ | / | ADSC-exos can enhance skin flap survival, promote neovascularization | Bai et al. [127] |
Abbreviation: iMSCs human iPSC differentiate into mesenchymal stem cells, PMSCs placenta tissue mesenchymal stem cells, EPCs endothelial progenitor cells, BM-MSCs bone marrow-mesenchymal stem cells, ADSCs adipose-derived stem cells, HUVECs human umbilical vein endothelial cells, VEGF vascular endothelial growth factor, IL-6 interleukin-6, HIF-1a hypoxia-inducible factor 1 alpha, TGF-β transforming growth factor beta, VEGF-A1 vascular endothelial growth factor A1, VEGF-A2 vascular endothelial growth factor A2, bFGF basic fibroblast growth factor, bFGFR basic fibroblast growth factor receptor, VEGF vascular endothelial growth factor, MMP-9 matrix metallopeptidase 9