Table 1.
Biological roles of stem/progenitor cell-derived extracellular vesicles
| Biological Effect | Mechanism of Action | Cell Source | Target | Reference |
|---|---|---|---|---|
| Regulation of stemness, self-renewal, and differentiation | – Transfer of proteins and mRNAs– Upregulation of pluripotency-related gene expression | Mouse embryonic stem cells | Hematopoietic progenitor cells | (119) |
| Proangiogenic effect | – Transfer of specific proteins, mRNAs and miRNAs (miR-126 and miR-296)– Activation of PI3K/Akt pathway– Inhibition of apoptosis | EPCs | Endothelial cells | (24, 49) |
| Improvement of myocardial function and regeneration after IRI | – Transfer of pluripotency-related miRNAs (e.g., miR-294)– Activation of PI3K/Akt pathway– Inhibition of apoptosis– Decreased oxidative stress and increased ATP and NADH production– Reduction of inflammation, infarct size, and fibrosis | MSCs, cardiomyocyte progenitor cells, mouse embryonic stem cells | Cardiomyocites, inflammatory cells | (3, 84, 141) |
| Improvement of renal function and regeneration after AKI | – Transfer of specific proteins, mRNAs, and miRNAs– Transfer of mRNA coding for IGF-1 receptor and HGF which increase cell proliferation– Inhibition of apoptosis– Reduction of inflammation | MSCs from bone marrow, renal glomeruli, Wharton’s jelly, umbilical cord, HLSCs, EPCs, and tubular progenitor cells | Renal tubular epithelial cells, inflammatory cells | (17, 18, 20, 21, 24, 33, 34, 63, 69, 80, 116, 136, 154) |
| Improvement of renal function in experimental anti-Thy1.1 glomerulonephritis | – Transfer of mRNA coding for the complement inhibitors Factor H, CD55 and CD59– Reduction of complement-mediated mesangial injury– Reduction of inflammation and histopathological changes | EPCs | Mesangial cells | (25) |
| Improvement of renal function in CKD (e.g., aristolochic acid-induced kidney fibrosis, DN) | – Transfer of specific miRNAs which downregulate pro-fibrotic genes– Transfer of VEGF, TGF-β1, angiogenin which increase glomerular cell proliferation– Transfer of BMP-7 which inhibits apoptosis– Reduction of fibrosis, inflammation, and histopathological changes | MSCs from bone marrow, urine, HLSCs | Renal fibrosis, podocytes and renal tubular epithelial cells | (62, 78, 85, 109) |
| Stimulation of liver regeneration after acute injury | – Transfer of specific mRNAs– Increase of hepatocyte proliferation and apoptosis resistance | HLSCs | Hepatocytes | (68) |
| Improvement of liver function and regeneration after chronic injury | – Increase of proliferation-related protein expression– Inhibition of apoptosis through upregulation of Bcl-xL– EMT inhibition– Reduction of fibrosis and inflammation | MSCs from umbilical cord and embryonic stem cells | Hepatic fibrosis | (91, 128) |
| Neuroprotective effect (e.g., Alzheimer’s disease, stroke) | – Transfer of specific miRNAs involved in axon regeneration (e.g., miR-17-92, miR-21, miR-133, miR-146a)– Transfer of long non-coding RNAs which increase cell proliferation(e.g., MALAT1)– Transfer of neprilysin which contributes to β-amyloid peptide clearance in the brain– Increase of angiogenesis and neurogenesis– Reduction of neuroinflammation | MSCs from adipose tissue and bone marrow | Glia, hippocampal neurons, retinal ganglion and neuroblastoma cells | (51, 83, 104, 145, 153) |
| Immunomodulation | – Increase of CD4+CD25+FoxP3+ Tregs which inhibit graft-versus-host disease– Reduction of Th17 and NK cells– Downregulation of Th1 responses– Upregulation of anti-inflammatory genes (e.g., TGF-β1 and IL-10)– Downregulation of proinflammatory genes (e.g., IL-1β, IL-12P40, IL-6 and tumor necrosis factor) | MSCs from bone marrow | CD4+ T cells, synovial leukocytes | (26, 150, 151) |
AKI, acute kidney injury; BMP-7, bone morphogenetic protein-7; CKD, chronic kidney disease; DN, diabetic nephropathy; EMT, epithelial-mesenchymal transition; EPCs, endothelial progenitor cells; HLSCs, human liver stem cells; IGF-1, insulin-like growth factor 1; IRI, ischemia-reperfusion injury; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; miRNAs, microRNAs; MSCs, mesenchymal stromal cells; NK, natural killer; PI3K, phosphatidylinositol 3-kinase; TGF-β1, transforming growth factor-β1; VEGF, vascular endothelial growth factor.