Generation of proximal tubule spheroids for nephrotoxicity assessment

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Title
Generation of proximal tubule spheroids for nephrotoxicity assessment
Author(s)
Dae Hun Kim; Jung Hwa LimCho-Rok JungHyun Mi Kang
Bibliographic Citation
Organoid, vol. e, pp. e30-e30
Publication Year
2022
Abstract
Background: To date, nephrotoxicity in new drug development has been evaluated through two-dimensional culture of representative cell lines, such as HK-2 and human proximal tubule epithelial cells (hPTECs). Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clinical trials due to nephrotoxicity, which means the current renal cell lines used in preclinical trials have limitations for the accurate detection of nephrotoxicity. Methods and Results: Here, we established proximal tubule cell lines from immortalized mixed primary renal cells and generated functional proximal tubule cell spheroids, which expressed all apical basolateral transporters and showed epithelial polarity. Moreover, they showed a more sensitive drug response than hPTECs, which have been commonly used as in vitro kidney models. Conclusion: Taken together, the proximal tubule cells described in this study provide a more stable, reproducible, and accurate in vitro kidney model for predicting nephrotoxicity, which could help early compound development.
Keyword
Proximal tubule cellsIn vitro kidney modelNephrotoxicityKidney spheroids
ISSN
2765-205X
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.51335/organoid.2022.2.e30
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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