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

Table 6.

Engineering EVs in AKI.

In Vivo Model EV-Source and Route of Administration EV Isolation Method EV Engineering Method EV Biological Effect References
IRI mouse model
Left renal pedicle clamping for 15, 30, and 45 min		 P-MSCs
(100 µg EV/dose)
Intravenous injection after 12 h from reperfusion		 UC Hydrophobic insertion of P-Selectin Binding Protein (PBP) coupled with Cyanine 5.5
  • -

    Nephroprotection

  • -

    Improvement of angiogenesis

  • -

    Repair of renal parenchyma

 [61]
Cisplatin mouse model
Subcutaneous cisplatin injection
(10 mg/kg)		 h-UC-MSCs and neutrophils
(1 × 1010 EV/dose)
Tail intravenous injection for 2 days		 -h-UC-MSC-EVs obtained via UC
-Neutrophil-EVs obtained via cold ultrasonication		 NEX obtained from ratio 1:1 of h-UC-MSC-EVs and neutrophil-EVs via sequential polycarbonate membrane extrusion
  • -

    Reduction of inflammation

  • -

    Inhibition of apoptosis and induction of proliferation

  • -

    CD47-mediated inhibition of macrophage uptake

 [62]
IRI mouse model
Ligation of left renal artery and vein with contralateral nephrectomy		 TECs
(100 mg EV/0,5 mL)
Single tail intravenous injection 12 h after the surgery 		UC Adenovirus transfection of TECs inducing CD26 overexpression
  • -

    Reduction of inflammatory cell infiltration by modulation of CXCR4

 [63]
IRI mouse model
Renal pedicle clamping for 25 min		 h-BM-MSCs
(100 µg EV/dose)
Intravenous injection 6 h after IRU		 UC Plasmid transfection to overexpress IDO
  • -

    Reduction of inflammatory infiltrates

  • -

    Inhibition of macrophage polarization

 [64]
IRI mouse model
Renal pedicle clamping for 35 min		 RAW macrophages
(200 µg EV/dose)
Intravenous injection after reperfusion and every 24 h three times		 UC CMV-MCSSV40-Neomycin IL-10 plasmid transfection with Lipofectamine
  • -

    Reduction of macrophage infiltration

  • -

    Attenuation of AKI-CKD transition

  • -

    Suppression of mTOR and improvement of mitophagy

 [65]
IRI and UUO mouse model
IRI: Renal pedicle clamping for 35 min
UUO: ligation of the left ureter and right ureter was not ligated		 Red blood cells
(100–150 µg EV/dose)
Multiple injections once a day for five consecutive days		 UC Engineering of EV surface with Kim-1 bound to LTH peptide and EV cargo with siRNA for P65 and Snail65
  • -

    Alleviation of tubulointerstitial inflammation

  • -

    Attenuation of AKI-CKD transition

 [66]
IRI mouse model
Renal pedicle clamping for 40 min		 P-MSCs
(100 µg EV/dose)
Intravenous injection into three sites 5 min after reperfusion		 UC Naïve EV combined with collagen matrix
  • -

    Induction of renal cell proliferation

  • -

    Stimulation of pro-angiogenic and anti-fibrotic activity

 [67]
Cisplatin mouse model
subcutaneous cisplatin injection
(18 mg/kg)		 h-UC-MSCs
(100 µg EV/dose)
Two intravenous injections at 24 and 48 h		 UC Bioreactor 3D
  • -

    Improvement of renal function

  • -

    Reduction of inflammation

[68]

Abbreviations: ultracentrifugation (UC), ischemia and reperfusion injury (IRI), unilateral ureteral obstruction (UUO), placental mesenchymal stromal cells (P-MCSs), umbilical cord MSCs (UC-MSCs), tubular epithelial cells (TECs), bone marrow mesenchymal stromal cells (BM-MSCs), acute kidney injury to chronic kidney disease (AKI-CKD), Interleukin 10 (IL-10).