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Optimization of Renal Organoid and Organotypic Culture for Vascularization, Extended Development, and Improved Microscopy Imaging
Published on: March 28, 2020
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Ascorbate protects human kidney organoids from damage induced by cell-free hemoglobin
Julie Bejoy1, Justin M Farry1,2, Eddie S Qian1
1Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Disease Models & Mechanisms
|November 9, 2023
Summary
Cell-free hemoglobin (CFH) in sepsis causes kidney damage. Ascorbate (vitamin C) significantly protected human kidney organoids from CFH-induced injury, suggesting a potential treatment for sepsis-associated acute kidney injury.
Area of Science:
- Nephrology
- Cell Biology
- Critical Care Medicine
Background:
- Sepsis-associated acute kidney injury (AKI) is a severe complication in critically ill patients, linked to high mortality.
- Cell-free hemoglobin (CFH), released during severe sepsis, is independently associated with mortality and causes tubular cell damage.
- Existing models have limitations in replicating the intact kidney environment for AKI studies.
Purpose of the Study:
- To investigate the toxic effects of CFH on human kidney organoids, modeling sepsis-associated AKI.
- To evaluate the protective potential of clinically available small molecules against CFH-induced kidney injury.
Main Methods:
- Human kidney organoids were cultured using 3D and transwell methods.
- Organoids were treated with CFH for 48 hours to induce injury.
- CFH-injured organoids were co-treated with ascorbate (vitamin C) or acetaminophen to assess protective effects.
Main Results:
- CFH treatment led to increased tubular toxicity, oxidative stress, mitochondrial fragmentation, and endothelial cell injury in kidney organoids.
- Co-treatment with ascorbate significantly reduced CFH-induced toxicity and preserved endothelial cells.
- Ascorbate also mitigated mitochondrial fragmentation, indicating a protective mechanism.
Conclusions:
- CFH induces significant damage to human kidney organoids, recapitulating key features of sepsis-associated AKI.
- Ascorbate (vitamin C) demonstrates a protective effect against CFH-induced kidney injury.
- These findings highlight ascorbate as a potential therapeutic agent for preventing or treating sepsis-associated AKI.
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