Using Mouse Kidney Organoid Model for Nephrotoxic Drug Screening

Abstract

The kidneys often experience adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early prediction of these influences is essential to facilitate the entry of new, safe drugs into the market. 3D organoids derived from mouse kidney tissue can be used to evaluate drug nephrotoxicity in a faster and more efficient manner compared to traditional methods. The establishment of a method to culture these kidney-like organs from mouse kidney tissue is an important step towards advancing our understanding of the mechanisms of nephrotoxicity.This study established mouse kidney organoid lines from mouse kidney tissue using an organoid culture system. The consistency of the organoids with the original kidney tissue was evaluated through histopathology, and the kidney-specific marker (NPHS1, PODXL, WT1, Calb1) expression levels were characterized using immunofluorescence (IF) and qPCR. The study also validated the use of the kidney organoids for evaluating nephrotoxicity by measuring ATP levels in response to nephrotoxic compounds (cisplatin, doxorubicin, and gemcitabine).This study reports the successful establishment of mouse kidney organoids within two weeks, with a maximum of seven passages. The expression of kidney-specific markers in the organoids was higher compared to the control group. The organoids also showed increased sensitivity to the drugs cisplatin and doxorubicin, with IC50 values 5 times lower than those of 2D cell lines.The mouse kidney organoids established in this study demonstrated the presence of kidney specific markers and were found to be an effective and biologically relevant model to study nephrotoxicity in vitro.