Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity
To rapidly assess healthy tissue toxicities induced by new anti-cancer therapies (i.e., radiation alone or in combination with drugs), there is a critical need for relevant and easy-to-use models. Consistent with the ethical desire to reduce the use of animals in medical research, we propose to moni...
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MDPI AG
2023-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/20/2435 |
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| author | Maxime Dubail Sophie Heinrich Lucie Portier Jessica Bastian Lucia Giuliano Lilia Aggar Nathalie Berthault José-Arturo Londoño-Vallejo Marta Vilalta Gael Boivin Ricky A. Sharma Marie Dutreix Charles Fouillade |
| author_facet | Maxime Dubail Sophie Heinrich Lucie Portier Jessica Bastian Lucia Giuliano Lilia Aggar Nathalie Berthault José-Arturo Londoño-Vallejo Marta Vilalta Gael Boivin Ricky A. Sharma Marie Dutreix Charles Fouillade |
| author_sort | Maxime Dubail |
| collection | DOAJ |
| description | To rapidly assess healthy tissue toxicities induced by new anti-cancer therapies (i.e., radiation alone or in combination with drugs), there is a critical need for relevant and easy-to-use models. Consistent with the ethical desire to reduce the use of animals in medical research, we propose to monitor lung toxicity using an ex vivo model. Briefly, freshly prepared organotypic lung slices from mice were irradiated, with or without being previously exposed to chemotherapy, and treatment toxicity was evaluated by analysis of cell division and viability of the slices. When exposed to different doses of radiation, this ex vivo model showed a dose-dependent decrease in cell division and viability. Interestingly, monitoring cell division was sensitive enough to detect a sparing effect induced by FLASH radiotherapy as well as the effect of combined treatment. Altogether, the organotypic lung slices can be used as a screening platform to rapidly determine in a quantitative manner the level of lung toxicity induced by different treatments alone or in combination with chemotherapy while drastically reducing the number of animals. Translated to human lung samples, this ex vivo assay could serve as an innovative method to investigate patients’ sensitivity to radiation and drugs. |
| first_indexed | 2024-03-10T21:22:06Z |
| format | Article |
| id | doaj.art-ef3dbdb660124597aecf336248a066ab |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:22:06Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ef3dbdb660124597aecf336248a066ab2023-11-19T16:02:05ZengMDPI AGCells2073-44092023-10-011220243510.3390/cells12202435Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced ToxicityMaxime Dubail0Sophie Heinrich1Lucie Portier2Jessica Bastian3Lucia Giuliano4Lilia Aggar5Nathalie Berthault6José-Arturo Londoño-Vallejo7Marta Vilalta8Gael Boivin9Ricky A. Sharma10Marie Dutreix11Charles Fouillade12Institut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceSBAI Department, Sapienza University of Rome, 00161 Rome, ItalyInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceGlobal Translational Science, Varian, a Siemens Healthineers Company, Palo Alto, CA 94304, USAGlobal Translational Science, Varian, a Siemens Healthineers Company, Palo Alto, CA 94304, USAGlobal Translational Science, Varian, a Siemens Healthineers Company, Palo Alto, CA 94304, USAInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceInstitut Curie, Inserm U1021-CNRS UMR 3347, Paris Saclay University, Centre Universitaire, 91405 Orsay Cedex, FranceTo rapidly assess healthy tissue toxicities induced by new anti-cancer therapies (i.e., radiation alone or in combination with drugs), there is a critical need for relevant and easy-to-use models. Consistent with the ethical desire to reduce the use of animals in medical research, we propose to monitor lung toxicity using an ex vivo model. Briefly, freshly prepared organotypic lung slices from mice were irradiated, with or without being previously exposed to chemotherapy, and treatment toxicity was evaluated by analysis of cell division and viability of the slices. When exposed to different doses of radiation, this ex vivo model showed a dose-dependent decrease in cell division and viability. Interestingly, monitoring cell division was sensitive enough to detect a sparing effect induced by FLASH radiotherapy as well as the effect of combined treatment. Altogether, the organotypic lung slices can be used as a screening platform to rapidly determine in a quantitative manner the level of lung toxicity induced by different treatments alone or in combination with chemotherapy while drastically reducing the number of animals. Translated to human lung samples, this ex vivo assay could serve as an innovative method to investigate patients’ sensitivity to radiation and drugs.https://www.mdpi.com/2073-4409/12/20/2435radiation toxicityFLASH radiotherapyorganotypic lung slicesex vivo modelcombined treatment |
| spellingShingle | Maxime Dubail Sophie Heinrich Lucie Portier Jessica Bastian Lucia Giuliano Lilia Aggar Nathalie Berthault José-Arturo Londoño-Vallejo Marta Vilalta Gael Boivin Ricky A. Sharma Marie Dutreix Charles Fouillade Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity Cells radiation toxicity FLASH radiotherapy organotypic lung slices ex vivo model combined treatment |
| title | Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity |
| title_full | Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity |
| title_fullStr | Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity |
| title_full_unstemmed | Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity |
| title_short | Lung Organotypic Slices Enable Rapid Quantification of Acute Radiotherapy Induced Toxicity |
| title_sort | lung organotypic slices enable rapid quantification of acute radiotherapy induced toxicity |
| topic | radiation toxicity FLASH radiotherapy organotypic lung slices ex vivo model combined treatment |
| url | https://www.mdpi.com/2073-4409/12/20/2435 |
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