Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models
The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accoun...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Online Access: | https://www.mdpi.com/2072-666X/13/1/3 |
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| author | Pengfei Yu Zhongping Duan Shuang Liu Ivan Pachon Jianxing Ma George P. Hemstreet Yuanyuan Zhang |
| author_facet | Pengfei Yu Zhongping Duan Shuang Liu Ivan Pachon Jianxing Ma George P. Hemstreet Yuanyuan Zhang |
| author_sort | Pengfei Yu |
| collection | DOAJ |
| description | The kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts for 1/4 of reported serious adverse reactions, and 1/3 of them are attributable to antibiotics. Drug-induced nephrotoxicity is driven by multiple mechanisms, including altered glomerular hemodynamics, renal tubular cytotoxicity, inflammation, crystal nephropathy, and thrombotic microangiopathy. Although the functional proteins expressed by renal tubules that mediate drug sensitivity are well known, current in vitro 2D cell models do not faithfully replicate the morphology and intact renal tubule function, and therefore, they do not replicate in vivo nephrotoxicity. The kidney is delicate and complex, consisting of a filter unit and a tubular part, which together contain more than 20 different cell types. The tubular epithelium is highly polarized, and maintaining cellular polarity is essential for the optimal function and response to environmental signals. Cell polarity depends on the communication between cells, including paracrine and autocrine signals, as well as biomechanical and chemotaxis processes. These processes affect kidney cell proliferation, migration, and differentiation. For drug disposal research, the microenvironment is essential for predicting toxic reactions. This article reviews the mechanism of drug-induced kidney injury, the types of nephrotoxicity models (in vivo and in vitro models), and the research progress related to drug-induced nephrotoxicity in three-dimensional (3D) cellular culture models. |
| first_indexed | 2024-03-10T00:55:28Z |
| format | Article |
| id | doaj.art-1daea6fe9a30420f94c3a4fa48b97d12 |
| institution | Directory Open Access Journal |
| issn | 2072-666X |
| language | English |
| last_indexed | 2024-03-10T00:55:28Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj.art-1daea6fe9a30420f94c3a4fa48b97d122023-11-23T14:43:23ZengMDPI AGMicromachines2072-666X2021-12-01131310.3390/mi13010003Drug-Induced Nephrotoxicity Assessment in 3D Cellular ModelsPengfei Yu0Zhongping Duan1Shuang Liu2Ivan Pachon3Jianxing Ma4George P. Hemstreet5Yuanyuan Zhang6Difficult & Complicated Liver Diseases and Artificial Liver Center, Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, ChinaDifficult & Complicated Liver Diseases and Artificial Liver Center, Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, ChinaDifficult & Complicated Liver Diseases and Artificial Liver Center, Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, ChinaWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USADepartment of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USAOmaha Veterans Administration Medical Center, Omaha, NE 68105, USAWake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USAThe kidneys are often involved in adverse effects and toxicity caused by exposure to foreign compounds, chemicals, and drugs. Early predictions of these influences are essential to facilitate new, safe drugs to enter the market. However, in current drug treatments, drug-induced nephrotoxicity accounts for 1/4 of reported serious adverse reactions, and 1/3 of them are attributable to antibiotics. Drug-induced nephrotoxicity is driven by multiple mechanisms, including altered glomerular hemodynamics, renal tubular cytotoxicity, inflammation, crystal nephropathy, and thrombotic microangiopathy. Although the functional proteins expressed by renal tubules that mediate drug sensitivity are well known, current in vitro 2D cell models do not faithfully replicate the morphology and intact renal tubule function, and therefore, they do not replicate in vivo nephrotoxicity. The kidney is delicate and complex, consisting of a filter unit and a tubular part, which together contain more than 20 different cell types. The tubular epithelium is highly polarized, and maintaining cellular polarity is essential for the optimal function and response to environmental signals. Cell polarity depends on the communication between cells, including paracrine and autocrine signals, as well as biomechanical and chemotaxis processes. These processes affect kidney cell proliferation, migration, and differentiation. For drug disposal research, the microenvironment is essential for predicting toxic reactions. This article reviews the mechanism of drug-induced kidney injury, the types of nephrotoxicity models (in vivo and in vitro models), and the research progress related to drug-induced nephrotoxicity in three-dimensional (3D) cellular culture models.https://www.mdpi.com/2072-666X/13/1/3drug-induced nephrotoxicitythree-dimensionalorganoidschipsin vitro modelsstem cells |
| spellingShingle | Pengfei Yu Zhongping Duan Shuang Liu Ivan Pachon Jianxing Ma George P. Hemstreet Yuanyuan Zhang Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models Micromachines drug-induced nephrotoxicity three-dimensional organoids chips in vitro models stem cells |
| title | Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models |
| title_full | Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models |
| title_fullStr | Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models |
| title_full_unstemmed | Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models |
| title_short | Drug-Induced Nephrotoxicity Assessment in 3D Cellular Models |
| title_sort | drug induced nephrotoxicity assessment in 3d cellular models |
| topic | drug-induced nephrotoxicity three-dimensional organoids chips in vitro models stem cells |
| url | https://www.mdpi.com/2072-666X/13/1/3 |
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