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Kidney Week

Abstract: PO0142

Multiple Beneficial Effects of Renal Exosomes on Ischemic Injury

Session Information

  • AKI Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kelly, Katherine J., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Dominguez, Jesus H., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

Ischemic injury to the kidney and other organs is deadly and expensive. We have demonstrated the effectiveness of adult cell-based therapies in multiple models of renal failure. Given the large benefits of relatively few cells, we hypothesized that exosomes from transplanted cells were the therapeutic effector. We and others have shown beneft with exosomes in renal injury models. To define the mechanisms of benefit from renal exosomes, the effects of exosomes from platelets and dermal epithelia were compared to those of renal exosomes.

Methods

The hypothesis that renal exosomes improve multiple pathways of injury postischemia and contain anti-oxidant and anti-inflammatory cargo was tested in a renal ischemia model. Exosomes from post-ischemic kidneys, platelets or skin were isolated by serial centrifugation. Renal function was estimated from serum creatinine. Oxidative stress and inflammation were assessed by immunostaining for 4-hydroxynoneal and neutrophils, respectively. Anti-inflammatory cytokine levels were measured by enzyme-linked immunoassay.

Results

We found significant improvements in renal function (figure) and structure with renal exosomes, given 24 hours postischemia, when renal failure was present. Exosomes from skin epithelia or platelets were not effective. Renal, but not skin or platelet, exosomes decreased evidence of oxidative stress in post-ischemic kidneys by 67%, with preservation of catalase and superoxide dismutase. Significantly less renal neutrophil infiltration was found in the renal exosome group as compared to postischemia groups that received vehicle or skin or platelet exosomes. Anti-inflammatory IL-10 levels were significantly higher in post-ischemic kidneys in the renal exosome group.

Conclusion

Exosomes derived from kidney cells effect multiple pathways of injury to improve postischemic kidney function.

Funding

  • Private Foundation Support