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] |