ATP/ADP biosensor organoids for drug nephrotoxicity assessment
Drug nephrotoxicity is a common healthcare problem in hospitalized patients and a major limitation during drug development. Multi-segmented kidney organoids derived from human pluripotent stem cells may complement traditional cell culture and animal experiments for nephrotoxicity assessment. Here we...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1138504/full |
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| author | Koichiro Susa Koichiro Susa Koichiro Susa Kenichi Kobayashi Kenichi Kobayashi Pierre Galichon Pierre Galichon Takuya Matsumoto Takuya Matsumoto Takuya Matsumoto Akitoshi Tamura Ken Hiratsuka Ken Hiratsuka Ken Hiratsuka Ken Hiratsuka Navin R. Gupta Navin R. Gupta Navin R. Gupta Iman K. Yazdi Iman K. Yazdi Iman K. Yazdi Iman K. Yazdi Joseph V. Bonventre Joseph V. Bonventre Joseph V. Bonventre Joseph V. Bonventre Ryuji Morizane Ryuji Morizane Ryuji Morizane Ryuji Morizane Ryuji Morizane |
| author_facet | Koichiro Susa Koichiro Susa Koichiro Susa Kenichi Kobayashi Kenichi Kobayashi Pierre Galichon Pierre Galichon Takuya Matsumoto Takuya Matsumoto Takuya Matsumoto Akitoshi Tamura Ken Hiratsuka Ken Hiratsuka Ken Hiratsuka Ken Hiratsuka Navin R. Gupta Navin R. Gupta Navin R. Gupta Iman K. Yazdi Iman K. Yazdi Iman K. Yazdi Iman K. Yazdi Joseph V. Bonventre Joseph V. Bonventre Joseph V. Bonventre Joseph V. Bonventre Ryuji Morizane Ryuji Morizane Ryuji Morizane Ryuji Morizane Ryuji Morizane |
| author_sort | Koichiro Susa |
| collection | DOAJ |
| description | Drug nephrotoxicity is a common healthcare problem in hospitalized patients and a major limitation during drug development. Multi-segmented kidney organoids derived from human pluripotent stem cells may complement traditional cell culture and animal experiments for nephrotoxicity assessment. Here we evaluate the capability of kidney organoids to investigate drug toxicity in vitro. Kidney organoids express renal drug transporters, OAT1, OAT3, and OCT2, while a human proximal tubular cell line shows the absence of OAT1 and OAT3. Tenofovir and aristolochic acid (AA) induce proximal tubular injury in organoids which is ameliorated by an OAT inhibitor, probenecid, without damage to podocytes. Similarly, cisplatin causes proximal tubular damage that can be relieved by an OCT inhibitor, cimetidine, collectively suggesting the presence of functional OATs and OCTs in organoid proximal tubules. Puromycin aminonucleoside (PAN) induced segment-specific injury in glomerular podocytes in kidney organoids in the absence of tubular injury. Reporter organoids were generated with an ATP/ADP biosensor, which may be applicable to high-throughput screening in the future. In conclusion, the kidney organoid is a useful tool for toxicity assessment in the multicellular context and may contribute to nephrotoxicity assessment during drug development. |
| first_indexed | 2024-04-10T06:22:11Z |
| format | Article |
| id | doaj.art-e2d18dd09a0142409faa4447a4bcf18a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T06:22:11Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-e2d18dd09a0142409faa4447a4bcf18a2023-03-02T04:19:11ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-03-011110.3389/fcell.2023.11385041138504ATP/ADP biosensor organoids for drug nephrotoxicity assessmentKoichiro Susa0Koichiro Susa1Koichiro Susa2Kenichi Kobayashi3Kenichi Kobayashi4Pierre Galichon5Pierre Galichon6Takuya Matsumoto7Takuya Matsumoto8Takuya Matsumoto9Akitoshi Tamura10Ken Hiratsuka11Ken Hiratsuka12Ken Hiratsuka13Ken Hiratsuka14Navin R. Gupta15Navin R. Gupta16Navin R. Gupta17Iman K. Yazdi18Iman K. Yazdi19Iman K. Yazdi20Iman K. Yazdi21Joseph V. Bonventre22Joseph V. Bonventre23Joseph V. Bonventre24Joseph V. Bonventre25Ryuji Morizane26Ryuji Morizane27Ryuji Morizane28Ryuji Morizane29Ryuji Morizane30Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Nephrology, Tokyo Medical and Dental University, Tokyo, JapanHarvard Medical School, Boston, MA, United StatesMassachusetts General Hospital, Boston, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesMassachusetts General Hospital, Boston, MA, United StatesWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesMassachusetts General Hospital, Boston, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United StatesDivision of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard-MIT Division of Health Sciences &Technology, Massachusetts Institute of Technology, Cambridge, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesDivision of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard-MIT Division of Health Sciences &Technology, Massachusetts Institute of Technology, Cambridge, MA, United StatesRenal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, United StatesHarvard Medical School, Boston, MA, United StatesMassachusetts General Hospital, Boston, MA, United StatesWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United StatesHarvard Stem Cell Institute, Cambridge, MA, United StatesDrug nephrotoxicity is a common healthcare problem in hospitalized patients and a major limitation during drug development. Multi-segmented kidney organoids derived from human pluripotent stem cells may complement traditional cell culture and animal experiments for nephrotoxicity assessment. Here we evaluate the capability of kidney organoids to investigate drug toxicity in vitro. Kidney organoids express renal drug transporters, OAT1, OAT3, and OCT2, while a human proximal tubular cell line shows the absence of OAT1 and OAT3. Tenofovir and aristolochic acid (AA) induce proximal tubular injury in organoids which is ameliorated by an OAT inhibitor, probenecid, without damage to podocytes. Similarly, cisplatin causes proximal tubular damage that can be relieved by an OCT inhibitor, cimetidine, collectively suggesting the presence of functional OATs and OCTs in organoid proximal tubules. Puromycin aminonucleoside (PAN) induced segment-specific injury in glomerular podocytes in kidney organoids in the absence of tubular injury. Reporter organoids were generated with an ATP/ADP biosensor, which may be applicable to high-throughput screening in the future. In conclusion, the kidney organoid is a useful tool for toxicity assessment in the multicellular context and may contribute to nephrotoxicity assessment during drug development.https://www.frontiersin.org/articles/10.3389/fcell.2023.1138504/fullnephronorganoidATPdrug developmenttransporterkidney |
| spellingShingle | Koichiro Susa Koichiro Susa Koichiro Susa Kenichi Kobayashi Kenichi Kobayashi Pierre Galichon Pierre Galichon Takuya Matsumoto Takuya Matsumoto Takuya Matsumoto Akitoshi Tamura Ken Hiratsuka Ken Hiratsuka Ken Hiratsuka Ken Hiratsuka Navin R. Gupta Navin R. Gupta Navin R. Gupta Iman K. Yazdi Iman K. Yazdi Iman K. Yazdi Iman K. Yazdi Joseph V. Bonventre Joseph V. Bonventre Joseph V. Bonventre Joseph V. Bonventre Ryuji Morizane Ryuji Morizane Ryuji Morizane Ryuji Morizane Ryuji Morizane ATP/ADP biosensor organoids for drug nephrotoxicity assessment Frontiers in Cell and Developmental Biology nephron organoid ATP drug development transporter kidney |
| title | ATP/ADP biosensor organoids for drug nephrotoxicity assessment |
| title_full | ATP/ADP biosensor organoids for drug nephrotoxicity assessment |
| title_fullStr | ATP/ADP biosensor organoids for drug nephrotoxicity assessment |
| title_full_unstemmed | ATP/ADP biosensor organoids for drug nephrotoxicity assessment |
| title_short | ATP/ADP biosensor organoids for drug nephrotoxicity assessment |
| title_sort | atp adp biosensor organoids for drug nephrotoxicity assessment |
| topic | nephron organoid ATP drug development transporter kidney |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1138504/full |
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