Table 2 Studies demonstrating the functional proteins in MSC-EVs
From: Functional proteins of mesenchymal stem cell-derived extracellular vesicles
References | Sources of MSC-EVs | Experimental model | Functional protein | Major findings |
|---|---|---|---|---|
Mokarizadeh et al. [53] | Mouse BM MSC-EVs | Mouse with experimental autoimmune encephalomyelitis | PD-L1, galectin-1, and TGF-β | MSC-EVs elevated the production of anti-inflammatory cytokines and the generation of regulatory T cells on splenic mononuclear cells. |
Crain et al. [54] | Wharton’s jelly MSC-EVs of dog | In vitro peripheral blood mononuclear cells | TGF-β | MSC-EVs suppressed CD4+ T cell proliferation via TGF-β. |
Alvarez et al. [55] | Human endometrial MSC-EVs | In vitro peripheral blood mononuclear cells | TGF-β | The immunomodulatory effect of MSC-EVs on CD4+ T cells is partially mediated by TGF-β. |
Adamo et al. [56] | Human BM MSC-EVs | Culture of B cells with inflammation-primed MSC-EVs | MOES, LG3BP, PTX3, and S10A6 | Inflammation-primed MSC-EVs modulated the PI3K-AKT signaling pathway of B cells and the actin cytoskeleton. |
Harting et al. [57] | Human BM MSC-EVs | Culture of splenocytes with MSC-EVs | Cox2 | EVs from inflammation-stimulated MSCs attenuated inflammation. |
Chen et al. [58] | Human BM MSC-EVs | Mouse model for inducible hippocampal CA1 neuron damage | IL-2, IL-10, RANTES, VEGF, and BDNF | EP4 antagonist induced the release of MSC-EVs and improved memory and learning deficiencies. |
Katsuda et al. [59] | Human adipose MSC-EVs | In vitro model of Alzheimer’s disease | Neprilysin | MSC-EVs carried enzymatically active neprilysin, which degrades β-amyloid peptide. |
de Godoy et al. [60] | Rat BM MSC-EVs | In vitro model of Alzheimer’s disease | Catalase | MSC-EVs protected neurons from β-amyloid peptide-induced oxidative stress via the transfer of catalase. |
McBride et al. [61] | Human BM MSC-EVs | Fibroblasts from a patient with epidermolysis bullosa | Type VII collagen | MSC-EVs transported type VII collagen protein and mRNA to fibroblasts. |
Zhang et al. [62] | Human umbilical cord MSC-EVs | Rat skin wound model | Wnt4 | MSC-EVs delivered Wnt4 to skin cells. Wnt4 enhanced wound healing and improved the survival of skin cells. |
Zhang et al. [63] | Human umbilical cord MSC-EVs | Rat skin wound model | 14-3-3ζ | MSC-EVs delivered 14-3-3ζ to keratinocytes and controlled the Wnt response via regulating YAP. |
Shabbir et al. [64] | Human BM MSC-EVs | In vitro model of wound healing | STAT3 | MSC-EVs enhanced the proliferation and migration of diabetic wound fibroblasts and augmented endothelial angiogenesis. |
Ahn et al. [65] | Human umbilical cord blood MSC-EVs | Neonatal rat hyperoxic lung injury | VEGF | MSC-EVs attenuated neonatal hyperoxic lung injuries via the transfer of VEGF, and the effect was lost in MSC-EVs with VEGF knockdown. |
Wang et al. [66] | Mouse BM MSC-EVs | In vitro LPS-induced endothelial cell injury | HGF | MSC-EVs stabilized endothelial barrier function via HGF, and the effect was blocked by knockdown of HGF. |
Gennai et al. [67] | Human BM MSC-EVs | Ex vivo human lung perfusion model | CD44 | MSC-EVs restored alveolar fluid clearance in donor human lung, and the effect was blocked by anti-CD44 antibody |
Hu et al. 2018 [68] | Human BM MSC-EVs | Injured lung microvascular endothelial cells | CD44 | MSC-EVs restored protein permeability in injured microvascular endothelial cells via CD44-mediated EV internalization. |
Eirin et al. [69] | Pig adipose autologous MSC-EVs | Pig model of renal artery stenosis | IL-10 | MSC-EVs attenuated renal inflammation and fibrosis, and the protection was blunted in IL-10-depleted MSC-EVs. |
Shen et al. [70] | Mouse BM MSC-EVs | Mouse ischemia/reperfusion model | CCR2 | MSC-EVs blocked macrophage functions and alleviated ischemia/reperfusion-induced renal injury via CCR2. |
Jiang et al. [71] | Human urine MSC-EVs | In vitro and in vivo model of diabetic nephropathy | VEGF, TGF-β, and angiogenin | MSC-EVs averted kidney complications from type I diabetes in rats by suppressing apoptosis and promoting angiogenesis. |
Ma et al. [72] | Human umbilical cord MSC-EVs | Rat model of acute myocardial infarction | PDGF-D | EVs derived from MSCs with AKT overexpression enhanced angiogenesis via PDGF-D. |
Gonzalez-King et al. [73] | Human dental pulp MSC-EVs | In vitro and in vivo model of angiogenesis | Jagged1 | HIF1-α overexpressing MSC-EVs promoted angiogenesis via elevated level of Jagged1. |
Vrijsen et al. [74] | Mouse BM MSC-EVs | In vitro and in vivo model of angiogenesis | EMMPRIN | MSC-EVs stimulated angiogenesis via elevated expression of EMMPRIN. |
Lopatina et al. [75] | Human adipose MSC-EVs | In vitro and in vivo model of angiogenesis | c-kit and SCF | EVs from PDGF-treated MSCs carried c-kit and SCF that displayed a role in angiogenesis. |
Wysoczynski et al. [76] | Human cardiac MSC-EVs | In vitro model of angiogenesis | Angiopoietins 1 and 2 | The pro-angiogenic effects of MSC-EVs were independent of RNA transfer and relied on packaged angiopoietins 1 and 2. |
Iglesias et al. [77] | Human amniotic fluid MSC-EVs | In vitro model of cystinosis | Cystinosin | MSC-EVs alleviated cystine accumulation in skin fibroblasts from cystinosis patients via the transfer of cystinosin. |
Mao et al. [78] | Mouse BM MSC-EVs | Mouse foregastric carcinoma in vitro and in vivo | UBR2 | UBR2 was enriched in MSC-EVs with p53 deficiency and promoted gastric cancer progression via the Wnt/β-catenin pathway. |