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. 2023 Jun 12;15(6):1715. doi: 10.3390/pharmaceutics15061715

Table 7.

Engineering EVs in CKD.

In Vivo Model EV-Source EV Isolation Method EV Route of Administration EV Biological Effect References
UUO mouse model
Ligation of the left ureter and right ureter was not ligated		 m-BM-MSCs
(30 µg EV/dose)
Tail intravenous injection 1 day after the surgery		 UC Two days of EPO incubation with m-BM-MSC and subsequent EPO-EVs isolation
  • -

    Improved renal function and histology

  • -

    Inhibition of EMT

  • -

    α-SMA downregulation

  • -

    Upregulation of E-cadherin expression

 [70]
UUO mouse model
Ligation of the left ureter and right ureter was not ligated		 h-BM-MSCs
(50 µg EV/dose)
Intravenous injection twice a week for 4 weeks		 GETTM Exosome isolation kit h-BM-MSC transfected with Let-7i-5p antagomir in presence of lipofectamine
  • -

    Attenuation of ECM deposition and EMT

  • -

    Amelioration of kidney function and histology

  • -

    Activation of TSC1/mTOR pathway

 [71]
UUO mouse model
Ligation of the left ureter and right ureter was not ligated		 h-A-MSCs
(1000 µg EV/dose)
Tail intravenous injection		 UC h-A-MSC lentiviral transfection with a vector plasmid system for GDNF gene
  • -

    Reduction of renal fibrosis and capillary rarefaction

  • -

    Improvement of angiogenesis

  • -

    Enhanced SIRT1 signaling

 [73]
CKD mouse model
Mice were fed with 0.25% adenine-containing diet		 h-A-MSCs
(50-100 µg EV/dose)
Tail intravenous injection for 2 weeks		 Exosome isolation kit h-A-MSCs were treated with melatonin (1µM/mL) and subsequentially Exocue were isolated
  • -

    Reduction of renal fibrosis

  • -

    Downregulation of pro-inflammatory cytokines

  • -

    Downregulation of pro-fibrotic miRNAs

  • -

    Increased expression of AQP2 AQP5

 [75]
STZ-DN rat model
Intraperitoneal injection of STZ (65 mg/kg)		 h-USCs
(100 μg EV/dose)
Multiple intravenous injections
once a week for 12 consecutive weeks		 Exo Quick-TC Lentiviral transfection of h-USCs
  • -

    VEGF-A downregulation

  • -

    Amelioration of podocyte damage

 [76]

Abbreviations: ultracentrifugation (UC), unilateral ureteral obstruction (UUO), streptozotocin diabetic nephropathy (STZ-DN), chronic kidney disease (CKD), bone marrow mesenchymal stromal cells (BM-MSCs), adipose mesenchymal stromal cells (A-MSCs), urinary stem cells, epithelial to mesenchymal transition (EMT).