Kidney organoid derived from renal tissue stem cells is a useful tool for histopathological assessment of nephrotoxicity in a cisplatin-induced acute renal tubular injury model

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  • Ueno Shota
    Division of Experimental Pathology, Department of Biomedical Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan Research and Development Division, Kikkoman Corporation, 338 Noda, Noda, Chiba 278-0037, Japan
  • Kokura Kenji
    Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
  • Kuromi Yasushi
    Animal Research Facility, Advanced Medicine & Translational Research Center, Organization for Research Initiative and Promotion, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
  • Osaki Mitsuhiko
    Division of Experimental Pathology, Department of Biomedical Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
  • Okada Futoshi
    Division of Experimental Pathology, Department of Biomedical Sciences, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan Chromosome Engineering Research Center, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
  • Kitamura Shinji
    Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
  • Ohbayashi Tetsuya
    Animal Research Facility, Advanced Medicine & Translational Research Center, Organization for Research Initiative and Promotion, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan

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<p> Organoids derived from renal tissue stem cells (KS cells) isolated from the S3 segment of adult rat nephrons have previously been developed and evaluated. However, data regarding the histopathological evaluation of these organoids are limited. Therefore, in this study, we performed histopathological examinations of the properties of these organoids and evaluated the nephrotoxicity changes induced by cisplatin treatment. We observe that the tubular structure of the organoids was generally lined by a single layer of cells, in concordance with previous findings. Microvilli were exclusively observed under electron microscopy on the luminal side of this tubular structure. Moreover, the luminal side of the tubular structure was positive for aquaporin-1 (Aqp1), a marker of the proximal renal tubule. Cisplatin treatment induced cell death and degeneration, including cytoplasmic vacuolation, in cells within the tubular structure of the organoids. Cisplatin toxicity is associated with the induction of γ-H2AX (a marker of DNA damage) and the drop of phospho-histone H3 (a marker of cell division) levels. During the nephrotoxicity assessment, the kidney organoids displayed various features similar to those of the natural kidney, suggesting that it is possible to use these organoids in predicting nephrotoxicity. The histological evaluation of the organoids in this study provides insights into the mechanisms underlying nephrotoxicity.</p>

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