Generation of proximal tubule spheroids for nephrotoxicity assessment
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 Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clini...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Organoid Society
2022-10-01
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| Series: | Organoid |
| Subjects: | |
| Online Access: | http://j-organoid.org/upload/pdf/organoid-2022-2-e30.pdf |
| _version_ | 1797768314929283072 |
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| author | Dae Hun Kim Jung Hwa Lim Cho-Rok Jung Hyun Mi Kang |
| author_facet | Dae Hun Kim Jung Hwa Lim Cho-Rok Jung Hyun Mi Kang |
| author_sort | Dae Hun Kim |
| collection | DOAJ |
| description | 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 Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clinical trials due to nephrotoxicity, which means the current renal cell lines used in preclinical trials have limitations for the accurate detection of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. |
| first_indexed | 2024-03-12T20:52:44Z |
| format | Article |
| id | doaj.art-00094c74d6b8485cb8068e22211e66b4 |
| institution | Directory Open Access Journal |
| issn | 2765-205X |
| language | English |
| last_indexed | 2024-03-12T20:52:44Z |
| publishDate | 2022-10-01 |
| publisher | The Organoid Society |
| record_format | Article |
| series | Organoid |
| spelling | doaj.art-00094c74d6b8485cb8068e22211e66b42023-08-01T00:42:00ZengThe Organoid SocietyOrganoid2765-205X2022-10-01210.51335/organoid.2022.2.e3042Generation of proximal tubule spheroids for nephrotoxicity assessmentDae Hun Kim0Jung Hwa Lim1Cho-Rok Jung2Hyun Mi Kang3 Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, KoreaBackground 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.http://j-organoid.org/upload/pdf/organoid-2022-2-e30.pdfproximal tubule cells kidney modelnephrotoxicitykidney spheroids |
| spellingShingle | Dae Hun Kim Jung Hwa Lim Cho-Rok Jung Hyun Mi Kang Generation of proximal tubule spheroids for nephrotoxicity assessment Organoid proximal tubule cells kidney model nephrotoxicity kidney spheroids |
| title | Generation of proximal tubule spheroids for nephrotoxicity assessment |
| title_full | Generation of proximal tubule spheroids for nephrotoxicity assessment |
| title_fullStr | Generation of proximal tubule spheroids for nephrotoxicity assessment |
| title_full_unstemmed | Generation of proximal tubule spheroids for nephrotoxicity assessment |
| title_short | Generation of proximal tubule spheroids for nephrotoxicity assessment |
| title_sort | generation of proximal tubule spheroids for nephrotoxicity assessment |
| topic | proximal tubule cells kidney model nephrotoxicity kidney spheroids |
| url | http://j-organoid.org/upload/pdf/organoid-2022-2-e30.pdf |
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