Table 3 Extracellular vesicles derived from stem cells promote angiogenesis in myocardial ischemia
EVs source | EVs type | EVs isolation | Experimental model (target cells/animal models) | Functional cargo | Molecules/pathways activated | Key functions/downstream genes | Reference |
|---|---|---|---|---|---|---|---|
CDCs | Exosomes | Differential centrifugation Exoquick Exosome Precipitation Solution Ultracentrifugation | In vitro (HMECs) In vivo (male SCID mice) | miR-146a | / | Enhanced angiogenesis and the density of micro-vessels both in vitro and in vivo | Ibrahim et al. [93] |
CDCs | Exosomes | Ultracentrifugation Exoquick exosome precipitation solution | In vitro (HUVECs) In vivo (male SCID-beige mice) | / | / | In vitro: stimulate angiogenesis in a HUVEC angiogenesis assay. In vivo: stimulated capillary reorganization. | Lang et al. [94] |
CDCs | Exosomes | Differential centrifugation Ultracentrifugation | In vitro (HUVECs) | miR-126, miR-130a, miR-210 | / | Speculate: miR-210→EENA3↓→ tube formation↑ miR-130a→GAX and HoxA5↓→ VEGF and VEGFR2↑→tube formation↑ miR-126→VEGF and bFGF↑, Spred-1↓→ tube formation↑ | Namazi et al. [95] |
CDCs | Exosomes | 450 nm pore membrane filtration PEG ultrafiltration Centrifugation | In vivo (female adult Yucatan mini-pigs/MI model) | / | / | decreased acute ischaemia-reperfusion injury, and halt chronic post-MI adverse remodeling in pigs | Gallet et al. [96] |
BM-MSCs | Exosomes | ExoQuick-TC reagent Centrifugation | In vitro (HUVECs) In vivo (female Sprague-Dawley rats/MI model) | / | / | Exosomes accounted for the cardioprotection through the formation of new blood vessels. | Teng et al. [97] |
BM-MSCs | Exosomes | ExoQuick-TC reagent | In vitro (HUVECs) In vivo (female Sprague-Dawley rats/MI model) | CXCR4 | PI3K/Akt signaling pathway | VEGF ↑ Cardiomyocyte survival↑ | Kang et al. [98] |
BM-MSCs | Exosomes | Differential centrifugation Ultracentrifugation | In vitro (HUVECs/HMECs) In vivo (male C57bl/6 mice) | EMMPRIN | ERK/Akt signaling pathway | EMMPRIN has powerful proangiogenic effects both in vitro and in vivo | Vrijsen et al. [99] |
UC-MSCs | Exosomes | Differential centrifugation 100 kDa molecular weight cut-off hollow fiber membrane Ultracentrifugation | In vitro (EA.hy926 cells) In vivo (male Sprague-Dawley rats/MI model) | / | / | protect myocardial cells and accelerate heart repair by angiogenesis after ischemic injury. | Zhao et al. [100] |
ADSCs | MVs | Differential centrifugation Ultracentrifugation | In vitro (HUVECs) In vivo (male C57BL/6 J mice and nude mice) | miR-31 | / | FIH1↓ | Kang et al. [101] |
EnMSCs | Exosomes | 0.22-μm pore membrane filtration Exosome isolation reagent Centrifugation | In vitro (HUVECs) In vivo (male Sprague-Dawley rats/MI model) | miR-21-5p | PTEN-Akt pathway | PTEN↓ Akt and VEGF↑ | Wang et al. [102] |
ESCs | Exosomes | Ultracentrifugation | In vitro (HUVECs) In vivo (male C57BL/6 mice/MI model) | / | / | In vitro: increased tube formation; In vivo: decreased infarct size. | Khan et al. [103] |
iPSC | MVs | Differential centrifugation Ultracentrifugation | In vitro (CECs) In vivo (C57BL/6 mice/MI model) | / | / | In vitro: EVs impart cytoprotective properties to cardiac cells In vivo: induce superior cardiac repair with regard to LV function and vascularization. | Adamiak et al. [104] |
iPSC-Pg iPSC-CM | Exosomes | Ultracentrifugation | In vitro (HUVECs) In vivo (nude mice/MI model) | / | / | EV may promote cell survival, proliferation of resident cardiac cells, and angiogenesis thereby improving left ventricular function. | EI Harane et al. [105] |
CD34+ cells | Exosomes | Differential centrifugation Ultracentrifugation | In vitro (HUVECs) In vivo (nude mice) | miR-126, miR-130a | / | In vitro: promote tube formation in HUVECs In vivo: induced the formation of vessel-like endothelial structures in corneal angiogenesis assays. | Sahoo et al. [106] |