Table 2 Extracellular vesicles derived from stem cells promote angiogenesis in chronic wound healing
EVs source | EVs type | EVs isolation | Experimental model (target cells/animal models) | Functional cargo | Molecules/pathways activated | Key functions/downstream genes | Reference |
|---|---|---|---|---|---|---|---|
BM-MSCs | Exosomes | Differential centrifugation Ultracentrifugation | In vitro (HUVECs) | STAT3 | Akt, ERK, and STAT3 | HGF, IL-6, IGF-1, NGF and SDF1↑ | Shabbir et al. [54] |
BM-MSCs | Exosomes | Differential centrifugation PEG-US-S purification Ultracentrifugation | In vitro (HUVECs) | Wnt3a | Wnt pathway | CD63+ exosomes are a significant carrier of exterior Wnt3a which results in angiogenesis in vitro. | McBride et al. [55] |
ADSCs | MVs | Differential centrifugation 100 KDa molecular filtration Ultracentrifugation | In vitro (HUVECs) In vivo (mice/full-thickness wounds model) | / | PI3K-AKT and ERK signaling pathways | VEGFA, PDGFA, EGF and bFGF↑ | Ren et al. [56] |
ADSCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HUVECs) In vivo (male BALB/c nude mice) | miR-125a | Speculated to Notch signaling pathways | proangiogenic genes Ang1 and Flk1 ↑ anti-angiogenic genes Vash1, TSP1 and DLL4 ↓ | Liang et al. [57] |
ADSCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HUVECs) In vivo (nude mice) | / | PKA signaling pathway | proangiogenesis gene Angpt1 and Flk1↑ VEGF↑ anti-angiogenic gene Vash1↓ | Xue et al. [58] |
UC-MSCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HMECs) In vivo (male C57BL/6 mice/full-thickness excisional skin wounds model) | miR-21-3p | PI3K/Akt and ERK1/2 signaling | PTEN and SPRY1↓ | Hu et al. [59] |
UC-MSCs | Exosomes | Differential centrifugation 100 kDa molecular weight cut-off (MWCO) hollow fiber membrane Ultracentrifugation | In vitro (EA.hy926 cells) In vivo(rats/deep second-degree burn wounds model) | Wnt4 | Wnt pathway | Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects. | Zhang et al. [60] |
PMSCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HMECs) In vivo (nude mice/auricle ischemic injury model) | / | / | PMSC-Exos enhanced angiogenesis in vitro and in vivo | Komaki et al. [61] |
iPSCs | Exosomes | MagCapture Exosome Isolation Kit | In vivo (male C57BLKS/J-Leprdb (db/db) mice/full-thickness excisional skin wounds and diabetes model) | / | / | iPSC-Exos significantly increased micro-vessel of full-thickness excisional skin wounds in diabetes mice | Kobayashi et al. [62] |
iPSCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HUVECs) In vivo (female Sprague-Dawley rats/full-thickness skin defect model) | / | / | iPSC-Exos can increase proliferation, migration, and tube formation of HUVECs in a dose-dependent manner | Zhang et al. [63] |
EPCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HMECs) In vivo(male Sprague-Dawley rats) | / | / | eNOS, IL-8, ANG-1, E-selectin, VEGFA, VEGFR-2, HIF- 1a, CXCL16 and PDGFA↑ PDGFB and MMP-9↓ | Li et al. [64] |
EPCs | Exosomes | Differential centrifugation 0.2-μm pore membrane filtration Ultracentrifugation | In vitro (HMECs) In vivo (male Sprague-Dawley rats/diabetic model) | / | / | aFGF, eNOS, IL-8, ANG-1, E-selectin, VEGFA, VEGFR-2 and CXCL-16↑ MMP-9↓ | Li et al. [65] |