Evaluation of cisplatin-induced injury in human kidney organoids.

American Journal of Physiology. Renal Physiology
Jenny L. M. DigbyVeronika Sander

Abstract

Acute kidney injury (AKI) remains a major global healthcare problem, and there is a need to develop human-based models to study AKI in vitro. Toward this goal, we have characterized induced pluripotent stem cell-derived human kidney organoids and their response to cisplatin, a chemotherapeutic drug that induces AKI and preferentially damages the proximal tubule. We found that a single treatment with 50 µM cisplatin induces hepatitis A virus cellular receptor 1 (HAVCR1) and C-X-C motif chemokine ligand 8 (CXCL8) expression, DNA damage (γH2AX), and cell death in the organoids but greatly impairs organoid viability. DNA damage was not specific to the proximal tubule but also affected the distal tubule and interstitial cell populations. This lack of specificity correlated with low expression of proximal tubule-specific SLC22A2/organic cation transporter 2 (OCT2) for cisplatin. To improve viability, we developed a repeated low-dose regimen of 4 × 5 µM cisplatin over 7 days and found this caused less toxicity while still inducing a robust injury response that included secretion of known AKI biomarkers and inflammatory cytokines. This work validates the use of human kidney organoids to model aspects of cisplatin-induced injury, with t...Continue Reading

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Citations

Jul 2, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Josephine C AdamsIrving H Zucker
Dec 31, 2020·STAR Protocols·Veronika SanderAlan J Davidson
May 30, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Andrew M HallRobert J Unwin
May 14, 2021·Clinical and Translational Science·Mitsuhiro GodaKeisuke Ishizawa
Aug 31, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Congchao JiaRong Chen

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BETA
PCR
Profiler
RNA-Seq
proteome array

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Trim Galore
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edgeR
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STAR
ImageJ
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