USD Conference Systems, International Conference on Sustainable Natural Products in Healthcare 2025

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Generation of Kidney Organoids as an Advance Kidney in Vitro Test Systems for Drug Induced-kidney Injury Assessment
Lukas Surya Wijaya

Last modified: 2025-05-07

Abstract


Developing in vitro kidney injury models remains a challenge due to the complex architecture of the organ. Here, we adapted the Takasato IPSC-derived kidney organoid protocol to generate an advanced multicellular high throughput in vitro test system for chemical-induced kidney injury model. We performed systematic evaluations of this test system to ensure the compatibility of the kidney organoids for toxicological purposes. Our results consistently indicated that the kidney organoids exhibited a coherent formation of nephron segments including podocytes, proximal tubule, and distal tubule. Moreover, the kidney organoids also showed clear cellular responses that reflected our understanding of in vivo mechanisms of nephrotoxicants e.g. cisplatin. We also employed the hiPSC endogenous CRISPR-Cas GFP-P21 reporter derived kidney organoids to capture live-temporal dynamic of the DNA damage responses in the proximal tubule upon cisplatin exposure. Altogether, we demonstrated the applicability domain of the kidney organoids for toxicological purposes with a potential as a high throughput test system to monitor chemical-induced nephrotoxicity.


Keywords


Kidney, hiPSC, organoids, transcriptomics, microscopy