Table 2 Summary of researches on EVs involved in in vivo wound repair
Wound type | Animal model | EVs type | Cargo | Target | Function | References |
|---|---|---|---|---|---|---|
Acute wound | Rat model of the skin-deep second-degree burn wound | HucMSC-derived EVs (30–100 nm) | – | Wnt/β-catenin | Proangiogenic effect↑ | [94] |
Rat skin burn model | HucMSC-derived EVs | – | Wnt4 | Heat stress-induced apoptosis↓ | [95] | |
Deep second-degree burn mice model | Blue light-treated MSC-derived EVs | miR-135b-5p miR-499a-3p | MEF2C | Proangiogenic ability↑ | [89] | |
Severe burn rat model | HucMSC-derived EVs | miR-181c | Toll-like receptor 4 | Burn-induced inflammation↓ | [96] | |
Rat full-thickness cutaneous wounds model | UCB-MSC-derived EVs | miR-21-5p miR-125b-5p | TGF-β receptor type II and TGF-β receptor type I | Anti-myofibroblast differentiation↑ | [91] | |
Mouse full-thickness cutaneous wounds model | UCMSC-derived EVs (75.66 nm) | – | – | Recruitment of fibroblasts↑ Cutaneous nerve regeneration↑ | [97] | |
Mouse full-thickness skin defects model | HucMSC-derived EVs (85% range from 20 to 200 nm) | – | Inhibiting nuclear translocation of apoptosis-inducing factor Upregulating poly ADP ribose polymerase 1 (PARP-1) and poly (ADP-ribose) | Epidermal re-epithelialization↑ Dermal angiogenesis↑ | [98] | |
Mouse skin wound model | BMSCs overexpressed with miR-126 EVs (Exo-miR-126, 30–200 nm) | miR-126 | Targeting phosphoinositol-3 kinase regulatory subunit 2 to activate the PI3K/Akt signalling pathway | Newly formed capillaries↑ | [24] | |
Rat skin wound model | hiPSC-MSC-derived EVs | – | – | Collagen synthesis↑ Angiogenesis↑ | [47] | |
Rat skin wound model | HucMSC-derived EVs | 14-3-3ζ proteins | Wnt/β-catenin signaling | Cutaneous regeneration | [99] | |
Mouse retinal laser injury wound model | HucMSC-derived EVs (40–100 nm) | – | Downregulation of monocyte chemotactic protein-1 | Apoptosis↓ Inflammatory responses↓ | [100] | |
Mouse full-thickness dermal wound injury model | FDMSC-derived EVs | – | Notch signaling pathway by Jagged 1 | Adult dermal fibroblast cell motility and secretion ability↑ | [101] | |
Mouse full-thickness dorsal wound model | ADMSC-derived EVs | – | Regulating the ratios of collagen type III to type I, TGF-β3 to TGF-β1 and MMP-3 to TIMP-1 | ECM reconstruction↑ | [102] | |
Mouse full-thickness dorsal wound model | ADMSC-derived EVs | miR-125a-3p | PTEN | Angiogenesis↑ | [103] | |
Corneal epithelial wound model | HucMSC-derived EVs | miR-21 | PTEN PI3K/Akt signaling pathway | Corneal wound repair↑ | [104] | |
Mouse excisional full-thickness wound model | ADMSC-derived EVs (113.6 nm) | miR-192-5p | miR-192-5p/IL-17RA/Smad axis | Anti-fibrotic properties↑ | [105] | |
Mouse full-thickness skin wound model | TSG-6 overexpressed MSC-derived EVs | – | – | Scar pathological injury↓ Collagen deposition↓ | [106] | |
Mouse full-thickness wound model | ADMSC-derived EVs | – | – | Collagen expression↓ Scar formation↓ | [107] | |
Mouse skin-defective wound model | BMSC-derived EVs (20–200 nm) | miR-223 | PKNOX1 | M2 polarization of macrophages | [108] | |
Mouse full-thickness skin defect model | HucMSC-derived EVs (30–150 nm) | miR-21 miR-23a miR-125b miR-145 | Transforming growth factor-β/Smad2 signaling pathway | Myofibroblast formation↓ | [109] | |
Murine hind limb ischemia model | EVs released from hP-MSCs by NO stimulation | VEGF miR-126 | – | Angiogenic processes↑ | [110] | |
Diabetic rat wound model | ATV pretreated BMSC (ATV-derived EVs, 80–120 nm) | miR-221-3p | Akt/eNOS signaling pathway | Angiogenesis effect↑ | [111] | |
Chronic wound | Diabetic rat wound model | HucMSC-derived EVs (30–150 nm) | – | – | VEGF and TGF-β1↑ | [112] |
Diabetic mouse cutaneous wound model | HucMSC-derived EVs (30–150 nm) | – | – | Oxidative stress↓ Angiogenesis↑ | [113] | |
Eczema mouse wound model | MSC-derived EVs | – | – | Inflammatory cell infiltration↓ Vascular formation↑ | [114] | |
Diabetic mouse wound model | Hypoxic ADMSC-derived EVs | Upregulated miR-21-3p, miR-126-5p, miR-31-5p Downregulated miR-99b and miR-146-a | PI3K/Akt signaling pathway | Diabetic wounds healing↑ Inflammation↓ | [115] | |
Diabetic rat cutaneous wound model | LPS‐preconditioning of HucMSC-derived EVs (40–90 nm) | let-7b | let-7b/TLR4 pathway[116] | Regulatory abilities for macrophage polarization | [116] | |
AD-like chronic allergic dermatitis mouse model | ADMSC-derived EVs | – | Facilitating the de novo synthesis of ceramides | Epidermal barrier functions↑ | [117] | |
Rat diabetic foot ulcers model | Linc00511-overexpressing ADMSC-derived EVs | – | Suppressing PAQR3-induced Twist1 ubiquitin degradation | Angiogenesis↑ | [118] | |
Diabetic rat wound model | hBMSC-derived EVs hBMSC-MT-derived EVs (30–150 nm) | – | PTEN/Akt pathway | Regulating macrophage M1 and M2 polarization | [26] | |
SD rat skin photoaging model | ADMSC-derived EVs (30–150 nm) | – | – | Type I collagen↑ Type III collagen, MMP-1, and MMP-3↓ | [119] | |
Wound model | ADMSCs overexpressing Nrf2-EVs | – | – | Granulation tissue formation↑ Angiogenesis↑ Growth factor expression↑ Oxidative stress-related proteins↓ | [120] | |
Diabetic mouse cutaneous wound model | BMSC-derived EVs (50–150 nm) | lncRNA KLF3-AS1 | miR-383, VEGFA | Angiogenesis↑ | [121] | |
Diabetic rat wound model | BMSCs preconditioned by deferoxamine-derived EVs (50–150 nm) | miR-126 | PTEN PI3K/Akt signaling pathway | Wound healing↑ Angiogenesis↑ | [122] | |
HucMSC-derived EVs (40–100 nm) | – | Downregulation of monocyte chemotactic protein-1 | Apoptosis↓ Inflammatory responses↓ | [100] |