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Intravascular Delivery of Biologics to the Rat Kidney
Published on: September 1, 2016
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Renal, but not platelet or skin, extracellular vesicles decrease oxidative stress, enhance nascent peptide synthesis,
Jesus H Dominguez1,2, Danhui Xie1, K J Kelly1,2
1Division of Nephrology and Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States.
American Journal of Physiology. Renal Physiology
|June 15, 2023
Summary
Organ-specific extracellular vesicles (EVs) show promise for treating acute kidney injury (AKI). Renal EVs, but not skin or platelet EVs, improved kidney function and reduced oxidative stress in a preclinical AKI model.
Area of Science:
- Nephrology
- Regenerative Medicine
- Cell Biology
Background:
- Acute kidney injury (AKI) presents a significant clinical challenge with limited therapeutic options beyond dialysis.
- Extracellular vesicles (EVs), including exosomes, are emerging as potential therapeutic agents.
- Previous studies suggested beneficial effects of renal cell-derived EVs in experimental AKI.
Purpose of the Study:
- To investigate the organ specificity of EV-mediated protection in ischemic acute kidney injury.
- To elucidate the underlying mechanisms by which renal EVs exert protective effects.
- To test if EVs from non-renal sources (skin, platelets) offer similar benefits.
Main Methods:
- Utilized a well-established ischemia-reperfusion model of acute kidney injury in rodents.
- Administered extracellular vesicles derived from renal cells, skin cells, or platelets after the onset of renal failure.
- Assessed renal function (e.g., creatinine levels), renal histology, oxidative stress markers (superoxide dismutase, catalase), and anti-inflammatory cytokine (interleukin-10) levels.
Main Results:
- Renal extracellular vesicles significantly improved renal function and histology post-ischemia, even when administered after established renal failure.
- Extracellular vesicles derived from skin or platelets did not confer similar protective effects.
- Renal EV treatment led to decreased oxidative stress, preserved key antioxidant enzymes, and increased interleukin-10 levels.
- A novel mechanism involving enhanced nascent peptide synthesis by renal EVs was proposed.
Conclusions:
- Organ-specific extracellular vesicles, particularly those derived from renal cells, demonstrate therapeutic potential for acute kidney injury.
- The protective effects are associated with reduced oxidative stress, enhanced anti-inflammatory responses, and potentially improved protein synthesis.
- These findings provide proof of principle for exploring renal EVs as a targeted therapy for AKI.
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