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Table 1 Anti-fibrotic effect of MSC-EVs in different models

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]
  1. MSCs, mesenchymal stem cells; EVs, extracellular vesicles; MSC-EVs, mesenchymal stem cell-derived extracellular vesicles; Exos, exosomes; MVs, microvesicles; BLM, Bleomycin; EndMT, Endothelial-mesenchymal transition; EMT, epithelial mesenchymal transition; CCl4, carbon tetrachloride; HSCs, hepatic stellate cells; NASH, nonalcoholic steatohepatitis; I/R, ischemia/reperfusion; STZ, streptozotocin; UUO, unilateral ureteral obstruction; TAC, transverse aortic constriction; MI, myocardial infarction; HSFs, hypertrophic scar-derived fibroblasts; IUA, intrauterine adhesion