Table 1.
Therapeutic applications of EVs in kidney disease
| Functional agent | EV origin | Animal model | Efficacy | Reference |
|---|---|---|---|---|
| Nucleic acid | ||||
| miR-34c-5p | BM-MSC | UUO | Reduced pericyte, fibroblast, and macrophage activation and renal fibrosis | [74] |
| I/R | ||||
| miR-186-5p agomir | MSC | UUO | Inhibited ECM accumulation and EMT process | [76] |
| miR-125a | AD-MSC | DN | Reduced mesangial hyperplasia, expansion of mesangial matrix, and kidney fibrosis | [77] |
| miR-26a-5p | HEK293 cell | UUO | Suppressed muscle wasting and renal fibrosis by targeting FoxO1 and CTGF | [79] |
| let-7i-5p antagomir | BM-MSC | UUO | Reduced renal fibrosis by activating the TSC1/ mTOR pathway | [80] |
| miR-16-5p | Urine-derived stem cells | DN | Improved diabetic nephropathy and inhibited podocyte apoptosis by reducing VEGF-A | [81] |
| miR-29 | Primary mouse satellite cell | UUO | Ameliorated skeletal muscle atrophy and attenuated kidney fibrosis | [82] |
| miR-20b-3p | AD-MSC | Ethylene glycol-induced hyperoxaluria | Reduced cell autophagy and inflammatory responses | [83] |
| miR-let7c | BM-MSC | UUO | Attenuated kidney injury and reduced ECM accumulation and fibrotic-related gene expression | [84] |
| siP65 and siSnai1 | Red blood cell | I/R-induced AKI or UUO | Alleviated tubulointerstitial inflammation and fibrosis and abrogated the transition to CKD | [75] |
| Oct-4 mRNA | UC-MSC | I/R | Increased the therapeutic effects of | [85] |
| MSC-EVs to attenuate kidney fibrosis | ||||
| Protein | ||||
| Klotho | Urine/fibroblast | AKI generated by glycerol injection | Accelerated renal recovery, stimulated tubular cell proliferation, and reduced inflammation; reduced renal retention and tissue injury; promoted amelioration of renal function | [86] |
| IL-10 protein | RAW264.7 cell | I/R-induced AKI | Ameliorated renal tubular injury and inflammation and prevented AKI-to-CKD transition | [73] |
| GDNF | AD-MSC | UUO | Ameliorated peritubular capillary loss in tubulointerstitial fibrosis | [87] |
| Super-repressor IκBα | HEK293T cell | CLP-induced sepsis | Attenuated mortality, acute organ injury, and inflammation by inhibiting the NF-κB pathway | [88] |
| Super-repressor IκBα | HEK293T cell | I/R-induced AKI | Alleviated renal damage and ameliorated inflammation and apoptosis | [89] |
| CD26 | TCMK1 cell | I/R-induced AKI | Protected against kidney injury by maintaining proliferation and dissipating inflammation | [90] |
| Erythropoietin | Kidney MSC | Model of CKD and renal anemia | Improved hemoglobin levels and renal function in CKD mice and exerted antifibrotic and anti-inflammatory effects | [91] |
| Small molecule | ||||
| Dexamethasone | RAW264.7 cell | LPS- or ADR-induced nephropathy | Suppressed renal inflammation and fibrosis without apparent glucocorticoid adverse effects | [72] |
AD, adipose mesenchymal stem cell; ADR, adriamycin; AKI, acute kidney injury; BM, bone marrow; CKD, chronic kidney disease; CLP, cecal ligation and puncture; CTGF, connective tissue growth factor; DN, diabetic nephropathy; ECM, extracellular matrix; EMT, epithelial-mesenchymal transition; EV, extracellular vesicle; GDNF, glial-derived neurotrophic factor; I/R, ischemia/reperfusion; LPS, lipopolysaccharide; mRNA, messenger RNA; MSC, mesenchymal stem cell; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor κB; UC, umbilical cord; UUO, unilateral ureteral obstruction; VEGF-A, vascular endothelial growth factor A.