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Transferability and reproducibility of exposed air-liquid interface co-culture lung models

Hedwig M. Braakhuis, Eric R. Gremmer, Anne Bannuscher, Barbara Drasler, Sandeep Keshavan, Barbara Rothen-Rutishauser, Barbara Birk, Andreas Verlohner, Robert Landsiedel, Kirsty Meldrum, Shareen Doak Orcid Logo, Martin Clift Orcid Logo, Johanna Samulin Erdem, Oda A.H. Foss, Shanbeh Zienolddiny-Narui, Tommaso Serchi, Elisa Moschini, Pamina Weber, Sabina Burla, Pramod Kumar, Otmar Schmid, Edwin Zwart, Jolanda P. Vermeulen, Rob J. Vandebriel

NanoImpact, Volume: 31, Start page: 100466

Swansea University Authors: Kirsty Meldrum, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

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DOI (Published version): 10.1016/j.impact.2023.100466

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Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI)...

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ISSN: 2452-0748
Published: Elsevier BV 2023
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fullrecord <?xml version="1.0" encoding="utf-8"?><rfc1807 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xsd="http://www.w3.org/2001/XMLSchema"><bib-version>v2</bib-version><id>63446</id><entry>2023-05-12</entry><title>Transferability and reproducibility of exposed air-liquid interface co-culture lung models</title><swanseaauthors><author><sid>bbb7bd27bfa3c6ffc73da8facfebc793</sid><firstname>Kirsty</firstname><surname>Meldrum</surname><name>Kirsty Meldrum</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>8f70286908f67238a527a98cbf66d387</sid><ORCID>0000-0002-6753-1987</ORCID><firstname>Shareen</firstname><surname>Doak</surname><name>Shareen Doak</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>71bf49b157691e541950f5c3f49c9169</sid><ORCID>0000-0001-6133-3368</ORCID><firstname>Martin</firstname><surname>Clift</surname><name>Martin Clift</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2023-05-12</date><deptcode>BMS</deptcode><abstract>Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a coculture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes).The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels.Results: Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO2) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO2 particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels.The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production.Conclusion: The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline.</abstract><type>Journal Article</type><journal>NanoImpact</journal><volume>31</volume><journalNumber/><paginationStart>100466</paginationStart><paginationEnd/><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>2452-0748</issnPrint><issnElectronic/><keywords>Inter-laboratory comparison, lung model, air-liquid exposure, nanomaterial, toxicity</keywords><publishedDay>1</publishedDay><publishedMonth>7</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-07-01</publishedDate><doi>10.1016/j.impact.2023.100466</doi><url>http://dx.doi.org/10.1016/j.impact.2023.100466</url><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>EU H2020: Project PATROLS (Physiologically Anchored Tools for Realistic nanomaterial hazard aSsessment), No. 760813</funders><projectreference>No. 760813</projectreference><lastEdited>2024-02-01T16:00:19.4725844</lastEdited><Created>2023-05-12T12:21:35.6322078</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>Hedwig M.</firstname><surname>Braakhuis</surname><order>1</order></author><author><firstname>Eric R.</firstname><surname>Gremmer</surname><order>2</order></author><author><firstname>Anne</firstname><surname>Bannuscher</surname><order>3</order></author><author><firstname>Barbara</firstname><surname>Drasler</surname><order>4</order></author><author><firstname>Sandeep</firstname><surname>Keshavan</surname><order>5</order></author><author><firstname>Barbara</firstname><surname>Rothen-Rutishauser</surname><order>6</order></author><author><firstname>Barbara</firstname><surname>Birk</surname><order>7</order></author><author><firstname>Andreas</firstname><surname>Verlohner</surname><order>8</order></author><author><firstname>Robert</firstname><surname>Landsiedel</surname><order>9</order></author><author><firstname>Kirsty</firstname><surname>Meldrum</surname><order>10</order></author><author><firstname>Shareen</firstname><surname>Doak</surname><orcid>0000-0002-6753-1987</orcid><order>11</order></author><author><firstname>Martin</firstname><surname>Clift</surname><orcid>0000-0001-6133-3368</orcid><order>12</order></author><author><firstname>Johanna Samulin</firstname><surname>Erdem</surname><order>13</order></author><author><firstname>Oda A.H.</firstname><surname>Foss</surname><order>14</order></author><author><firstname>Shanbeh</firstname><surname>Zienolddiny-Narui</surname><order>15</order></author><author><firstname>Tommaso</firstname><surname>Serchi</surname><order>16</order></author><author><firstname>Elisa</firstname><surname>Moschini</surname><order>17</order></author><author><firstname>Pamina</firstname><surname>Weber</surname><order>18</order></author><author><firstname>Sabina</firstname><surname>Burla</surname><order>19</order></author><author><firstname>Pramod</firstname><surname>Kumar</surname><order>20</order></author><author><firstname>Otmar</firstname><surname>Schmid</surname><order>21</order></author><author><firstname>Edwin</firstname><surname>Zwart</surname><order>22</order></author><author><firstname>Jolanda P.</firstname><surname>Vermeulen</surname><order>23</order></author><author><firstname>Rob J.</firstname><surname>Vandebriel</surname><order>24</order></author></authors><documents><document><filename>63446__28078__cc626675215b4f45943b70e991b4a00a.pdf</filename><originalFilename>63446.pdf</originalFilename><uploaded>2023-07-11T13:44:47.9773547</uploaded><type>Output</type><contentLength>3773109</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© 2023 The Authors. 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spelling v2 63446 2023-05-12 Transferability and reproducibility of exposed air-liquid interface co-culture lung models bbb7bd27bfa3c6ffc73da8facfebc793 Kirsty Meldrum Kirsty Meldrum true false 8f70286908f67238a527a98cbf66d387 0000-0002-6753-1987 Shareen Doak Shareen Doak true false 71bf49b157691e541950f5c3f49c9169 0000-0001-6133-3368 Martin Clift Martin Clift true false 2023-05-12 BMS Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a coculture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes).The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels.Results: Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO2) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO2 particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels.The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production.Conclusion: The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline. Journal Article NanoImpact 31 100466 Elsevier BV 2452-0748 Inter-laboratory comparison, lung model, air-liquid exposure, nanomaterial, toxicity 1 7 2023 2023-07-01 10.1016/j.impact.2023.100466 http://dx.doi.org/10.1016/j.impact.2023.100466 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee EU H2020: Project PATROLS (Physiologically Anchored Tools for Realistic nanomaterial hazard aSsessment), No. 760813 No. 760813 2024-02-01T16:00:19.4725844 2023-05-12T12:21:35.6322078 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Hedwig M. Braakhuis 1 Eric R. Gremmer 2 Anne Bannuscher 3 Barbara Drasler 4 Sandeep Keshavan 5 Barbara Rothen-Rutishauser 6 Barbara Birk 7 Andreas Verlohner 8 Robert Landsiedel 9 Kirsty Meldrum 10 Shareen Doak 0000-0002-6753-1987 11 Martin Clift 0000-0001-6133-3368 12 Johanna Samulin Erdem 13 Oda A.H. Foss 14 Shanbeh Zienolddiny-Narui 15 Tommaso Serchi 16 Elisa Moschini 17 Pamina Weber 18 Sabina Burla 19 Pramod Kumar 20 Otmar Schmid 21 Edwin Zwart 22 Jolanda P. Vermeulen 23 Rob J. Vandebriel 24 63446__28078__cc626675215b4f45943b70e991b4a00a.pdf 63446.pdf 2023-07-11T13:44:47.9773547 Output 3773109 application/pdf Version of Record true © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/) true eng http://creativecommons.org/licenses/bync-nd/4.0/
title Transferability and reproducibility of exposed air-liquid interface co-culture lung models
spellingShingle Transferability and reproducibility of exposed air-liquid interface co-culture lung models
Kirsty Meldrum
Shareen Doak
Martin Clift
title_short Transferability and reproducibility of exposed air-liquid interface co-culture lung models
title_full Transferability and reproducibility of exposed air-liquid interface co-culture lung models
title_fullStr Transferability and reproducibility of exposed air-liquid interface co-culture lung models
title_full_unstemmed Transferability and reproducibility of exposed air-liquid interface co-culture lung models
title_sort Transferability and reproducibility of exposed air-liquid interface co-culture lung models
author_id_str_mv bbb7bd27bfa3c6ffc73da8facfebc793
8f70286908f67238a527a98cbf66d387
71bf49b157691e541950f5c3f49c9169
author_id_fullname_str_mv bbb7bd27bfa3c6ffc73da8facfebc793_***_Kirsty Meldrum
8f70286908f67238a527a98cbf66d387_***_Shareen Doak
71bf49b157691e541950f5c3f49c9169_***_Martin Clift
author Kirsty Meldrum
Shareen Doak
Martin Clift
author2 Hedwig M. Braakhuis
Eric R. Gremmer
Anne Bannuscher
Barbara Drasler
Sandeep Keshavan
Barbara Rothen-Rutishauser
Barbara Birk
Andreas Verlohner
Robert Landsiedel
Kirsty Meldrum
Shareen Doak
Martin Clift
Johanna Samulin Erdem
Oda A.H. Foss
Shanbeh Zienolddiny-Narui
Tommaso Serchi
Elisa Moschini
Pamina Weber
Sabina Burla
Pramod Kumar
Otmar Schmid
Edwin Zwart
Jolanda P. Vermeulen
Rob J. Vandebriel
format Journal article
container_title NanoImpact
container_volume 31
container_start_page 100466
publishDate 2023
institution Swansea University
issn 2452-0748
doi_str_mv 10.1016/j.impact.2023.100466
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
url http://dx.doi.org/10.1016/j.impact.2023.100466
document_store_str 1
active_str 0
description Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a coculture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes).The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels.Results: Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO2) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO2 particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels.The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production.Conclusion: The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline.
published_date 2023-07-01T16:00:20Z
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