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

Table 4.

HLSC-EVs in CKD.

In Vivo Model EV-Source EV Isolation Method EV Route of Administration EV Biological Effect/
Mechanism of Action		 References
STZ-DN mouse model
Intraperitoneal injection of STZ (37 mg/kg) for 4 consecutive days		 HLSCs
(1 × 1010 EV/dose)		 UC Multiple intravenous injections once a week for 4 weeks starting from day 30 after diabetes onset
  • -

    Reduced renal fibrosis

  • -

    Reduced plasma levels of BUN and creatinine

  • -

    Reduced expression of pro-fibrotic and pro-inflammatory genes

 [46]
AAN mouse model
Intraperitoneal injection of 4 mg/kg of AA on a weekly basis for 4 weeks		 HLSCs
(1 × 1010 EV/dose)		 UC Multiple intravenous injections on a weekly basis starting from 3 days after AA administration
  • -

    Reduced tubular necrosis

  • -

    Reduced interstitial fibrosis

  • -

    Reduced infiltration of CD45+ cells

  • -

    Down-regulation of pro-fibrotic genes

 [57]
IRI mouse model
30 min IRI with contralateral nephrectomy		 HLSCs
(1 × 109 EV/dose)		 UC Two intravenous injections: one immediately after the surgery and one after three days
  • -

    Reduced creatinine plasma levels

  • -

    Reduced development of interstitial fibrosis

  • -

    Reduced expression of pro-inflammatory and pro-fibrotic genes

  • -

    Modulation of genes involved in the EMT process

 [44]

Abbreviations: ultracentrifugation (UC), Streptozotocin diabetic nephropathy (STZ-DN), Aristolochic acid nephropathy (AAN), human liver stem cells (HLSCs), ischemia and reperfusion injury (IRI).