From: Mesenchymal stem cell-derived extracellular vesicles in therapy against fibrotic diseases
Organ | Model | Animal | In vitro model | Administration | Dosage | Source of EVs/Exos/MVs | Cargo in EVs | Mechanism | Effect | Refs. |
---|---|---|---|---|---|---|---|---|---|---|
Lung | BLM | C57BL/6 J mice | MLE-12 cells with TGF-β1 | Tail vein | 0.5 mg/kg/day for 7 days | MenSC-Exos | miR-let-7 | ↓LOX1 | Regulating ROS, mtDNA damage, and NLRP3 inflammasome activation | [12] |
 | BLM | C57BL/6 mice | LL29 | Tail vein | 100 μg | BMMSC–EVs | miR-29b-3p | ↓FZD6 | Inhibiting fibroblast proliferation, migration, and differentiation | [13] |
 | BLM | C57BL/6 mice | LL29 | Tail vein | 100 μg | BMMSC–EVs | miR-186 | ↓SOX4 and DKK1 | Restraining fibroblast activation | [14] |
 | BLM | C57BL/6 mice |  | Tail vein | 8.6 × 108 particles | BMMSC–EVs |  |  | Modulating monocyte phenotypes | [15] |
 | Radiotherapy | C57 mice |  | Tail vein | 100 μg | hpMSC-EVs | miR-214-3p | ↓ATM/P53/P21 |  | [16] |
 | Pulmonary artery hypertension | Wistar rats | Pulmonary artery endothelial cells | Tail vein | 25 µg for 3 days | huMSC-Exos |  | Wnt5a/BMP | Inhibiting EndMT | [17] |
 | PM2.5 | SD rats | Type II alveolar epithelial cells | Intratracheal instillation | 2.5 ~ 2.8 × 1010 particles | ADMSC-EVs | miR-let-7d-5p | ↓TGF-βRI |  | [18] |
 | Lipopolysaccharide | C57BL/6 mice | MLE-12 cells | Tail vein | 70 μg | BMMSC-Exos | miR-23a-3, miR-182-5p | ↓NF-κB and hedgehog pathways via silencing Ikbkb and Usp5 | Reversing EMT | [19] |
Liver | CCl4 | Mice | HL7702 with TGF-β1 | Right lobes of livers | 250 mg | huMSC-Exos |  | ↓TGF-β1/Smad signalling pathway | Inhibiting EMT | [20] |
 | CCl4 | SD rats | Human HSCs line LX2 |  |  | CPMSC-Exos | miR-125b | ↓Hedgehog signalling | Suppressing activation of HSCs | [21] |
 | CCl4 | C57BL/6 J mice | HSCs with TGF-β | Tail vein |  | ADMSC-EVs | miR-150-5p | ↓CXCL1 |  | [22] |
 | CCl4 | SD rats | HSCs | Tail vein | 250 mg | BMMSC-Exos |  | ↓Wnt/β-catenin signalling pathway | Inhibition of HSCs | [23] |
 | NASH; CCl4 | SD rats | HSCs and KCs | Intravenous | 15/20 μg/kg | AMSC-EVs |  | ↓LPS/TLR4 signalling pathway | ↓Activation of HSCs and Kupffer cells | [24] |
 | NASH | SCID mice |  | Tail vein | 2.5 × 108 particles | HLSC-EVs | 251 proteins |  | ↓Inflammation and cytokine pathways | [25] |
Kidney | I/R | C57BL/6 mice | mTECs | Tail vein | 100ug | ADMSC-Exos |  | ↑Sox9 |  | [26] |
 | STZ | Babl/c mice | HK-2 | Tail vein | 1.5 mg/kg | huMSC-MVs | miR-451a | ↓P15 and P19 | Inhibiting EMT | [27] |
 | STZ | NSG mice |  | Intravenous | 1 × 1010 particles | HLSC/BMMSC-EVs | miRNAs | Fibrosis-related genes |  | [28] |
 | Aristolochic acid | NSG mice | mTECs | Intravenous | 1 × 1010 particles | BMMSC-EVs |  | ↓α-SMA, TGF-β1 and Col1a1 genes |  | [29] |
 | High glucose |  | MPC5 cells |  |  | ADMSC-Exos | miR-215-5p | ↓ZEB2 | Reversing EMT | [30] |
 | UUO | C57BL/6 J mice | NRK52E |  |  | BMMSC-Exos | miR-let7c | ↓TGF-βR1 |  | [31] |
 | UUO | SD rats |  | Tail vein | 10 mg/kg | huMSC-Exos | CK1δ/β-TRCP | ↓YAP |  | [32] |
 | UUO | SD rats | NRK-52E cells with TGF-β1 | Renal artery | 200 μg | huMSC-EVs |  | ↓ROS-mediated P38MAPK/ERK signalling pathway |  | [33] |
 | UUO | SD rats | HK-2 cells with TGF-β1 | Intravenous | 0.5 mg/kg | BMMSC-EVs | MFG-E8 | ↓RhoA/ROCK signalling |  | [34] |
Heart | TAC | C57BL/6 mice | NRVCs with AngII | Intramyocardial | 20 μL | BMMSC-Exos |  |  | ↑Senescence of myofibroblasts | [35] |
 | MI | Mice | HL-1 cardiac muscle cells |  | 0.5 μmol | BMMSC-Exos | miR-19a/19b |  |  | [36] |
 | MI | Rats | H9c2 cells with hypoxia | Inferior vena cava | 2.5 × 1012 particles | ADMSC-Exos |  | ↑S1P/SK1/S1PR1 signalling |  | [37] |
 | MI | C57BL/6JNifdc mice | Cardiomyocytes with OGD | Boundary area of the infarcted cardiac | 100 μg | ADMSC-Exos | miR-671 | TGFβR2/Smad2 |  | [38] |
Skin | Full-thickness skin defect | ICR and nude mice | Fibroblasts with TGF-β | Inject around the wound | 100 mg/ml | huMSC-Exos | miR-21, -23a, -125b, -145 | ↓TGF-β/Smad2 pathway | ↓Myofibroblast differentiation | [39] |
 | Full-thickness skin defect | BALB/c mice | Dermal fibroblasts | Intravenous | 200 μL | ADMSC-Exos |  | ↑MMP3 expression via ERK/MAPK pathway | Regulating ratios of type III: type I collagens, TGF-β3: TGF-β1, and MMP3:TIMP1 and fibroblast differentiation | [40] |
 | Full-thickness skin defect | C57BL/6 mice |  | Intradermal | 10 μg | MenSC-Exos |  |  | ↓Col1: Col3 ratio | [41] |
 | Full-thickness skin defect | BALB/c mice | HSFs | Subcutaneous | 70 μg | ADMSC-Exos | miR-192-5p / | Regulating Smad signalling pathway via IL-17RA | ↓The proliferation and migration of HSFs, decreased collagen deposition | [42] |
 | Sclerodermatous cGVHD | BALB/c mice |  | Intraperitoneal | 100 μg | huMSC-EVs |  | ↓TGF-β/smad2 | ↓The activation of macrophages and B cells immune response | [43] |
Uterus | IUA | ICR mice | Endometrial epithelial cells | Uterine cavity | 100μL | BMMSC-Exos | miR-29a |  | ↑Endometrial repair | [44] |
 | IUA | SD rats | Endometrial stromal cells | Tail vein |  | BMMSC-Exos | miR-340 | ↓col1α1, TGF-β1 and α-SMA expression |  | [45] |
 | IUA | Rabbits | Endometrial epithelial cells with TGF-β1 | Muscle walls of the uterus | 50 μg | BMMSC-Exos |  | ↓TGF-β1/Smad pathway | Reverse EMT | [46] |
Tendon | Tendon adhesion | SD rats | Fibroblast cells with TGF-β1 | Subcutaneous | 200 μg | huMSC-Exos | miR-21a-3p | ↓p65 |  | [47] |
Colon | TNBS | SD rats | IEC-6 Cells with TGF-β1 | Intravenous | 10 μg/day for 6 days | BMMSC-MVs | miR-200b | ↓ZBE1 and ZEB2 | Inhibiting EMT | [48] |