Journal article 1539 views 277 downloads
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure
Samantha Llewellyn,
Gill Conway 
,
Ume-kulsoom Shah ,
Stephen Evans ,
Gareth Jenkins ,
Martin Clift ,
shareen Doak
,
Ume-kulsoom Shah ,
Stephen Evans ,
Gareth Jenkins ,
Martin Clift ,
shareen Doak
Journal of Visualized Experiments, Issue: 160, Start page: e61141
Swansea University Authors:
Samantha Llewellyn, Gill Conway , Ume-kulsoom Shah , Stephen Evans , Gareth Jenkins , Martin Clift , shareen Doak
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DOI (Published version): 10.3791/61141
Abstract
Due to the rapid development and implementation of a diverse array of engineered nanomaterials (ENM), exposure to ENM is inevitable and the development of robust, predictive in vitro test systems is essential. Hepatic toxicology is key when considering ENM exposure, as the liver serves a vital role...
| Published in: | Journal of Visualized Experiments |
|---|---|
| ISSN: | 1940-087X |
| Published: |
MyJoVE Corporation
2020
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa54416 |
| first_indexed |
2020-06-09T19:09:21Z |
|---|---|
| last_indexed |
2025-04-08T03:57:42Z |
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Hepatic toxicology is key when considering ENM exposure, as the liver serves a vital role in metabolic homeostasis and detoxification as well as being a major site of ENM accumulation post exposure. Based upon this and the accepted understanding that 2D hepatocyte models do not accurately mimic the complexities of intricate multi-cellular interactions and metabolic activity observed in vivo, there is a greater focus on the development of physiologically relevant 3D liver models tailored for ENM hazard assessment purposes in vitro. In line with the principles of the 3Rs to replace, reduce and refine animal experimentation, a 3D HepG2 cell-line based liver model has been developed, which is a user friendly, cost effective system that can support both extended and repeated ENM exposure regimes (≤14 days). These spheroid models (≥500 µm in diameter) retain their proliferative capacity (i.e., dividing cell models) allowing them to be coupled with the ‘gold standard’ micronucleus assay to effectively assess genotoxicity in vitro. Their ability to report on a range of toxicological endpoints (e.g., liver function, (pro-)inflammatory response, cytotoxicity and genotoxicity) has been characterized using several ENMs across both acute (24 h) and long-term (120 h) exposure regimes. This 3D in vitro hepatic model has the capacity to be utilized for evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner.</abstract><type>Journal Article</type><journal>Journal of Visualized Experiments</journal><volume/><journalNumber>160</journalNumber><paginationStart>e61141</paginationStart><paginationEnd/><publisher>MyJoVE Corporation</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>1940-087X</issnElectronic><keywords/><publishedDay>5</publishedDay><publishedMonth>6</publishedMonth><publishedYear>2020</publishedYear><publishedDate>2020-06-05</publishedDate><doi>10.3791/61141</doi><url/><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>External research funder(s) paid the OA fee (includes OA grants disbursed by the Library)</apcterm><funders>The authors would like to acknowledge that this research has received funding from the European Union’s Horizon 2020 research and innovation programme for the PATROLS project, under grant agreement No.760813</funders><projectreference>760813</projectreference><lastEdited>2025-04-07T15:13:15.9022501</lastEdited><Created>2020-06-09T14:54:15.8119036</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Samantha</firstname><surname>Llewellyn</surname><order>1</order></author><author><firstname>Gill</firstname><surname>Conway</surname><orcid>0000-0002-5991-0960</orcid><order>2</order></author><author><firstname>Ume-kulsoom</firstname><surname>Shah</surname><orcid>0000-0002-0594-580X</orcid><order>3</order></author><author><firstname>Stephen</firstname><surname>Evans</surname><orcid>0000-0002-5352-9800</orcid><order>4</order></author><author><firstname>Gareth</firstname><surname>Jenkins</surname><orcid>0000-0002-5437-8389</orcid><order>5</order></author><author><firstname>Martin</firstname><surname>Clift</surname><orcid>0000-0001-6133-3368</orcid><order>6</order></author><author><firstname>shareen</firstname><surname>Doak</surname><order>7</order></author></authors><documents><document><filename>54416__17755__10838b55639f4f91b8dc7b893862d109.pdf</filename><originalFilename>54416.pdf</originalFilename><uploaded>2020-07-22T16:12:40.4181673</uploaded><type>Output</type><contentLength>808249</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>Copyright © 2020 Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported
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2025-04-07T15:13:15.9022501 v2 54416 2020-06-09 Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure fb4b6c686b654c6687c4063974b5cc8c Samantha Llewellyn Samantha Llewellyn true false e33e0ee5a076ad91fe6615117caa1800 0000-0002-5991-0960 Gill Conway Gill Conway true false bcef4e069220a4b85f8a2c0cc3059487 0000-0002-0594-580X Ume-kulsoom Shah Ume-kulsoom Shah true false cfca981bdfb8492873a48cc1629def9a 0000-0002-5352-9800 Stephen Evans Stephen Evans true false a44095d26187304e903da7ca778697b6 0000-0002-5437-8389 Gareth Jenkins Gareth Jenkins true false 71bf49b157691e541950f5c3f49c9169 0000-0001-6133-3368 Martin Clift Martin Clift true false 8f70286908f67238a527a98cbf66d387 shareen Doak shareen Doak true false 2020-06-09 MEDS Due to the rapid development and implementation of a diverse array of engineered nanomaterials (ENM), exposure to ENM is inevitable and the development of robust, predictive in vitro test systems is essential. Hepatic toxicology is key when considering ENM exposure, as the liver serves a vital role in metabolic homeostasis and detoxification as well as being a major site of ENM accumulation post exposure. Based upon this and the accepted understanding that 2D hepatocyte models do not accurately mimic the complexities of intricate multi-cellular interactions and metabolic activity observed in vivo, there is a greater focus on the development of physiologically relevant 3D liver models tailored for ENM hazard assessment purposes in vitro. In line with the principles of the 3Rs to replace, reduce and refine animal experimentation, a 3D HepG2 cell-line based liver model has been developed, which is a user friendly, cost effective system that can support both extended and repeated ENM exposure regimes (≤14 days). These spheroid models (≥500 µm in diameter) retain their proliferative capacity (i.e., dividing cell models) allowing them to be coupled with the ‘gold standard’ micronucleus assay to effectively assess genotoxicity in vitro. Their ability to report on a range of toxicological endpoints (e.g., liver function, (pro-)inflammatory response, cytotoxicity and genotoxicity) has been characterized using several ENMs across both acute (24 h) and long-term (120 h) exposure regimes. This 3D in vitro hepatic model has the capacity to be utilized for evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner. Journal Article Journal of Visualized Experiments 160 e61141 MyJoVE Corporation 1940-087X 5 6 2020 2020-06-05 10.3791/61141 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) The authors would like to acknowledge that this research has received funding from the European Union’s Horizon 2020 research and innovation programme for the PATROLS project, under grant agreement No.760813 760813 2025-04-07T15:13:15.9022501 2020-06-09T14:54:15.8119036 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Samantha Llewellyn 1 Gill Conway 0000-0002-5991-0960 2 Ume-kulsoom Shah 0000-0002-0594-580X 3 Stephen Evans 0000-0002-5352-9800 4 Gareth Jenkins 0000-0002-5437-8389 5 Martin Clift 0000-0001-6133-3368 6 shareen Doak 7 54416__17755__10838b55639f4f91b8dc7b893862d109.pdf 54416.pdf 2020-07-22T16:12:40.4181673 Output 808249 application/pdf Version of Record true Copyright © 2020 Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License true |
| title |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure |
| spellingShingle |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure Samantha Llewellyn Gill Conway Ume-kulsoom Shah Stephen Evans Gareth Jenkins Martin Clift shareen Doak |
| title_short |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure |
| title_full |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure |
| title_fullStr |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure |
| title_full_unstemmed |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure |
| title_sort |
Advanced 3D Liver Models for In vitro Genotoxicity Testing Following Long-Term Nanomaterial Exposure |
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fb4b6c686b654c6687c4063974b5cc8c e33e0ee5a076ad91fe6615117caa1800 bcef4e069220a4b85f8a2c0cc3059487 cfca981bdfb8492873a48cc1629def9a a44095d26187304e903da7ca778697b6 71bf49b157691e541950f5c3f49c9169 8f70286908f67238a527a98cbf66d387 |
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fb4b6c686b654c6687c4063974b5cc8c_***_Samantha Llewellyn e33e0ee5a076ad91fe6615117caa1800_***_Gill Conway bcef4e069220a4b85f8a2c0cc3059487_***_Ume-kulsoom Shah cfca981bdfb8492873a48cc1629def9a_***_Stephen Evans a44095d26187304e903da7ca778697b6_***_Gareth Jenkins 71bf49b157691e541950f5c3f49c9169_***_Martin Clift 8f70286908f67238a527a98cbf66d387_***_shareen Doak |
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Samantha Llewellyn Gill Conway Ume-kulsoom Shah Stephen Evans Gareth Jenkins Martin Clift shareen Doak |
| author2 |
Samantha Llewellyn Gill Conway Ume-kulsoom Shah Stephen Evans Gareth Jenkins Martin Clift shareen Doak |
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Journal of Visualized Experiments |
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160 |
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e61141 |
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2020 |
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1940-087X |
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10.3791/61141 |
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MyJoVE Corporation |
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Faculty of Medicine, Health and Life Sciences |
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Due to the rapid development and implementation of a diverse array of engineered nanomaterials (ENM), exposure to ENM is inevitable and the development of robust, predictive in vitro test systems is essential. Hepatic toxicology is key when considering ENM exposure, as the liver serves a vital role in metabolic homeostasis and detoxification as well as being a major site of ENM accumulation post exposure. Based upon this and the accepted understanding that 2D hepatocyte models do not accurately mimic the complexities of intricate multi-cellular interactions and metabolic activity observed in vivo, there is a greater focus on the development of physiologically relevant 3D liver models tailored for ENM hazard assessment purposes in vitro. In line with the principles of the 3Rs to replace, reduce and refine animal experimentation, a 3D HepG2 cell-line based liver model has been developed, which is a user friendly, cost effective system that can support both extended and repeated ENM exposure regimes (≤14 days). These spheroid models (≥500 µm in diameter) retain their proliferative capacity (i.e., dividing cell models) allowing them to be coupled with the ‘gold standard’ micronucleus assay to effectively assess genotoxicity in vitro. Their ability to report on a range of toxicological endpoints (e.g., liver function, (pro-)inflammatory response, cytotoxicity and genotoxicity) has been characterized using several ENMs across both acute (24 h) and long-term (120 h) exposure regimes. This 3D in vitro hepatic model has the capacity to be utilized for evaluating more realistic ENM exposures, thereby providing a future in vitro approach to better support ENM hazard assessment in a routine and easily accessible manner. |
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2020-06-05T04:44:24Z |
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11.089572 |