Renal, but Not Platelet or Skin, Extracellular Vesicles Decrease Oxidative Stress, Enhance Nascent Peptide Synthesis, and Protect from Ischemic Renal Injury

Acute kidney injury (AKI) is deadly and expensive, and specific, effective therapy remains a large unmet need. We have demonstrated the beneficial effects of transplanted adult tubular cells and exosomes derived from those renal cells on experimental ischemic AKI, even when administered after renal failure is established. To further examine the mechanisms of benefit, we tested the hypothesis that exosomes from other epithelia or platelets (a rich source of exosomes) might be protective, using a well-characterized ischemia/reperfusion model. Even when given after renal failure was present, renal exosomes, but not those from skin or platelets, markedly improved renal function and histology. The differential effects allowed us to examine the mechanisms of benefit with renal exosomes. We found significant decreases in oxidative stress postischemia in the renal exosome treated group with preservation of renal superoxide dismutase and catalase. In addition, we propose a novel mechanism of benefit: renal exosomes enhanced nascent peptide synthesis following hypoxia in cells and in postischemic kidneys. Although exosomes have been used therapeutically, these results serve as "proof of principle," to examine mechanisms of injury and protection.